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Effectiveness of Exercise on Fatigue and Sleep Quality in Fibromyalgia: A Systematic Review and Meta-analysis of Randomized Trials

Open AccessPublished:July 25, 2020DOI:https://doi.org/10.1016/j.apmr.2020.06.019

      Highlights

      • Exercise has moderate effects for lowering fatigue and small effects for enhancing sleep quality.
      • To augment its effectiveness, exercise may be better when it is specifically designed for the primary outcome of interest.
      • Exercise may be ideally designed when it is personalized to the patient’s characteristics and priorities.

      Abstract

      Objectives

      To determine the effects of exercise on fatigue and sleep quality in fibromyalgia (primary aim) and to identify which type of exercise is the most effective in achieving these outcomes (secondary aim).

      Data Sources

      PubMed and Web of Science were searched from inception until October 18, 2018.

      Study Selection

      Eligible studies contained information on population (fibromyalgia), intervention (exercise), and outcomes (fatigue or sleep). Randomized controlled trials (RCT) testing the effectiveness of exercise compared with usual care and randomized trials (RT) comparing the effectiveness of 2 different exercise interventions were included for the primary and secondary aims of the present review, respectively. Two independent researchers performed the search, screening, and final eligibility of the articles. Of 696 studies identified, 17 RCTs (n=1003) were included for fatigue and 12 RCTs (n=731) for sleep. Furthermore, 21 RTs compared the effectiveness of different exercise interventions (n=1254).

      Data Extraction

      Two independent researchers extracted the key information from each eligible study.

      Data Synthesis

      Separate random-effect meta-analyses were performed to examine the effects from RCTs and from RTs (primary and secondary aims). Standardized mean differences (SMD) effect sizes were calculated using Hedges’ adjusted g. Effect sizes of 0.2, 0.4, and 0.8 were considered small, moderate, and large. Compared with usual care, exercise had moderate effects on fatigue and a small effect on sleep quality (SMD, –0.47; 95% confidence interval [CI], –0.67 to –0.27; P<.001 and SMD, –0.17; 95% CI, –0.32 to –0.01; P=.04). RTs in which fatigue was the primary outcome were the most beneficial for lowering fatigue. Additionally, meditative exercise programs were the most effective for improving sleep quality.

      Conclusions

      Exercise is moderately effective for lowering fatigue and has small effects on enhancing sleep quality in fibromyalgia. Meditative exercise programs may be considered for improving sleep quality in fibromyalgia.

      Keywords

      List of abbreviations:

      CI (confidence interval), RCT (randomized controlled trial), RT (randomized trial), SMD (standardized mean difference)
      More than 80% of people with fibromyalgia experience severe fatigue
      • Overman C.L.
      • Kool M.B.
      • Da Silva J.a.P.
      • Geenen R.
      The prevalence of severe fatigue in rheumatic diseases: an international study.
      or poor sleep quality,
      • Bigatti S.M.
      • Hernandez A.M.
      • Cronan T.A.
      • Rand K.L.
      Sleep disturbances in fibromyalgia syndrome: relationship to pain and depression.
      both of which are identified by people with fibromyalgia and health care providers as priority targets for treatment. Increased fatigue and poor sleep quality are therefore acknowledged as core symptoms in the updated fibromyalgia diagnostic criteria.
      • Wolfe F.
      • Clauw D.J.
      • Fitzcharles M.-A.
      • et al.
      The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity.
      Despite the importance of fatigue and sleep quality, most of the research to date has traditionally focused on pain-related outcomes. For instance, the European League Against Rheumatism highlights that exercise is the only therapy supported by “strong” evidence for the management of fibromyalgia.
      • Macfarlane G.J.
      • Kronisch C.
      • Dean L.E.
      • et al.
      EULAR revised recommendations for the management of fibromyalgia.
      However, the recommendations were based on previous reviews that provided evidence of the benefits of exercise for pain but were unclear for other symptoms
      • Busch A.J.
      • Schachter C.L.
      • Overend T.J.
      • Peloso P.M.
      • Barber K.A.R.
      Exercise for fibromyalgia: a systematic review.
      • Bidonde J.
      • Busch A.J.
      • Schachter C.L.
      • et al.
      Aerobic exercise training for adults with fibromyalgia.
      • Bidonde J.
      • Busch A.J.
      • van der Spuy I.
      • Tupper S.
      • Kim S.Y.
      • Boden C.
      Whole body vibration exercise training for fibromyalgia.
      • Busch A.J.
      • Webber S.C.
      • Richards R.S.
      • et al.
      Resistance exercise training for fibromyalgia.
      • Busch A.
      • Schachter C.L.
      • Peloso P.M.
      • Bombardier C.
      Exercise for treating fibromyalgia syndrome.
      In their earliest works, Busch et al performed comprehensive reviews including all types of exercise (eg, aerobic, resistance, and flexibility training).
      • Busch A.J.
      • Schachter C.L.
      • Overend T.J.
      • Peloso P.M.
      • Barber K.A.R.
      Exercise for fibromyalgia: a systematic review.
      ,
      • Busch A.
      • Schachter C.L.
      • Peloso P.M.
      • Bombardier C.
      Exercise for treating fibromyalgia syndrome.
      These reviews concluded that the effects of exercise on fatigue or sleep were unknown owing to the paucity of research at that time. A number of subsequent systematic reviews focused on specific types of exercise have been published (ie, flexibility,
      • Kim S.Y.
      • Busch A.J.
      • Overend T.J.
      • et al.
      Flexibility exercise training for adults with fibromyalgia.
      aerobic,
      • Bidonde J.
      • Busch A.J.
      • Schachter C.L.
      • et al.
      Aerobic exercise training for adults with fibromyalgia.
      resistance,
      • Busch A.J.
      • Webber S.C.
      • Richards R.S.
      • et al.
      Resistance exercise training for fibromyalgia.
      and vibration
      • Bidonde J.
      • Busch A.J.
      • van der Spuy I.
      • Tupper S.
      • Kim S.Y.
      • Boden C.
      Whole body vibration exercise training for fibromyalgia.
      training), which have explored the effects of exercise on fatigue and sleep quality, among other outcomes. Although the contribution of these reviews to the evidence base is acknowledged, the decision to narrow the scope of each review resulted in the inclusion of a restricted number of studies. For instance, for fatigue, only 4 and 2 studies were included in the reviews by Bidonde et al
      • Bidonde J.
      • Busch A.J.
      • Schachter C.L.
      • et al.
      Aerobic exercise training for adults with fibromyalgia.
      and by Busch et al,
      • Busch A.J.
      • Webber S.C.
      • Richards R.S.
      • et al.
      Resistance exercise training for fibromyalgia.
      respectively. Consequently, it is difficult to make robust conclusions about the effects of exercise interventions on fatigue and sleep in fibromyalgia. Compared with previous reviews, a recent systematic review has focused on mixed exercise training (ie, 2 or more types of exercise combined).
      • Bidonde J.
      • Busch A.J.
      • Schachter C.L.
      • et al.
      Mixed exercise training for adults with fibromyalgia.
      This review included a larger number of studies (ie, 11 studies conducted with a total sample of 493 adults with fibromyalgia) and concluded that the effect of mixed exercise resulted in improvements in fatigue, but omitted study of sleep quality.
      • Bidonde J.
      • Busch A.J.
      • Schachter C.L.
      • et al.
      Mixed exercise training for adults with fibromyalgia.
      To date, no review has summarized all relevant literature on the effectiveness of exercise interventions (of any type) on fatigue and sleep quality in fibromyalgia. In doing so, the current review will include a large sample size and accurately estimate, for the first time, the effects of physical exercise on these 2 outcomes.
      The aims of this systematic review were to determine the effectiveness of exercise for reducing fatigue and improving sleep quality in people with fibromyalgia (primary aim) and to identify which type of exercise interventions might be the most effective in achieving these outcomes (secondary aim).

      Methods

      A multidisciplinary international task force was established to conduct this review. The PRISMA guidelines were used to guide this systematic review and meta-analysis.
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • Altman D.G.
      PRISMA Group
      Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
      The protocol of the present review was specified in advance and registered in the PROSPERO database (registration number: CRD42018118005).

      Data sources and searches

      PubMed and Web of Science were searched from inception until October 18, 2018. Search terms used in PubMed were "Fibromyalgia"[MeSH] AND ("Exercise"[MeSH]) OR “Training”[All Fields]) OR "Yoga"[MeSH]) OR "Tai Ji"[MeSH]) OR "Qigong"[MeSH]) OR “Hydrotherapy"[MeSH]) OR "body awareness"[Title/Abstract]) OR danc∗[Title/Abstract]). For Web of Science, the search terms were TI=(fibromyalgia) AND TI=("exercise" OR "training" OR "yoga" OR "tai chi" OR "tai ji" OR qigong OR hydrotherapy OR "physical activity" OR "body awareness" OR danc∗).

      Study selection

      Two independent researchers (F.E.-L. and C.M.-C.) performed the search, screened the titles and abstracts of all retrieved articles, and examined the final eligibility of the full-text articles. When a study did not report data on fatigue or sleep quality but used questionnaires including these outcomes, the authors were contacted for further information. No restrictions were applied for language. This review followed the PICOS framework.

      Population

      Adults with fibromyalgia who were diagnosed using 1 of the recognized American College of Rheumatology criteria (1990, 2010, 2011, or 2016) were included in this study.

      Intervention (exposure)

      Intervention was based on exercise. Mixed interventions that consisted of exercise combined with other interventions (ie, cointerventions) were considered, as long as exercise comprised at least 50% of the intervention.

      Comparison

      Studies should have either an intervention group with exercise and a non-intervention control group (eg, treatment as usual) or 2 exercise groups. Therefore, the primary subset of studies included randomized controlled trials (RCT) and the second subset of studies included randomized trials (RT).

      Outcome

      Outcomes measured were fatigue and sleep quality. When a study included more than 1 assessment per outcome, all the figures were extracted but only the most common assessment among the included studies was meta-analyzed.

      Study design

      RCTs and RTs were included for the primary and secondary aims, respectively.

      Data extraction and quality assessment

      Two independent researchers (C.M.-C. and D.R.) extracted the key information from each eligible study. When the information to be extracted was unavailable, authors were contacted. Disagreements were solved in a consensus meeting between the independent reviewers with a third reviewer (C.M.H.).
      The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess the quality of the evidence across studies for fatigue and sleep quality separately. Risk of bias of individual studies was assessed using the Cochrane Risk of Bias tool. Studies with a score of at least 5 points were considered as having high risk of bias. Inconsistency across studies was considered serious when heterogeneity was high (I2 ≥50%). Indirectness was considered serious when interventions included both exercise and additional components (ie, cointerventions). Imprecision was considered serious when the 95% confidence interval (CI) was wide and crossed the line of no effect, and as such the interpretation of the data would be different if the true effect were at 1 end of the CI or the other. Finally, publication bias was assessed via funnel plots.
      Two researchers independently assessed risk of bias (I.C.A.-G. and M.R.-A.) and the inconsistency, indirectness, imprecision, and publication bias (F.E.-L. and J.G.M.) of each eligible study. Disagreements on these assessments were solved in a consensus meeting between the independent reviewers with a third reviewer (C.M.H.).

      Data synthesis and analysis

      For the primary aim, quantitative synthesis of RCTs (ie, meta-analyses) were performed using Review Manager version 5.3.a Statistical significance was set at a P value less than .05. Standardized mean differences (SMD) between the exercise and control groups were computed for both outcomes separately. When a control group was used as a comparator twice in the same study, we halved the sample size of the control group. Weighted mean differences were calculated using a random effects model. Heterogeneity was measured using the I2 statistic (the percentage of total variability attributed to between-study heterogeneity). When heterogeneity was high (I2 ≥50%), further explorations based on subgroups analyses were computed. SMD effect sizes were calculated using Hedges’ adjusted g (similar to Cohen’s d). Effect sizes of 0.2, 0.4, and 0.8 were considered small, moderate, and large, respectively.
      For the secondary aim, a narrative synthesis structured around each outcome was conducted. When at least 3 of the included studies presented similar comparisons, we performed meta-analyses using the same methods that have been described for the primary aim.

      Results

      Study selection and characteristics

      Thirty-seven unique studies were included in this review.
      • Alentorn-Geli E.
      • Padilla J.
      • Moras G.
      • Lazaro Haro C.
      • Fernandez-Sola J.
      Six weeks of whole-body vibration exercise improves pain and fatigue in women with fibromyalgia.
      • Carson J.W.
      • Carson K.M.
      • Jones K.D.
      • Bennett R.M.
      • Wright C.L.
      • Mist S.D.
      A pilot randomized controlled trial of the Yoga of Awareness program in the management of fibromyalgia.
      • Tomas-Carus P.
      • Gusi N.
      • Hakkinen A.
      • Hakkinen 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.
      • Tomas-Carus P.
      • Hakkinen A.
      • Gusi N.
      • Leal A.
      • Hakkinen K.
      • Ortega-Alonso A.
      Aquatic training and detraining on fitness and quality of life in fibromyalgia.
      • Valkeinen H.
      • Alen M.
      • Hakkinen A.
      • Hannonen P.
      • Kukkonen-Harjula K.
      • Hakkinen K.
      Effects of concurrent strength and endurance training on physical fitness and symptoms in postmenopausal women with fibromyalgia: a randomized controlled trial.
      • van Santen M.
      • Bolwijn P.
      • Verstappen F.
      • et al.
      A randomized clinical trial comparing fitness and biofeedback training versus basic treatment in patients with fibromyalgia.
      • Wigers S.H.
      • Stiles T.C.
      • Vogel P.A.
      Effects of aerobic exercise versus stress management treatment in fibromyalgia. A 4.5 year prospective study.
      • Wong A.
      • Figueroa A.
      • Sanchez-Gonzalez M.A.
      • Son W.-M.
      • Chernykh O.
      • Park S.-Y.
      Effectiveness of tai chi on cardiac autonomic function and symptomatology in women with fibromyalgia: a randomized controlled trial.
      • Bircan C.
      • Karasel S.A.
      • Akgun B.
      • El O.
      • Alper S.
      Effects of muscle strengthening versus aerobic exercise program in fibromyalgia.
      • Calandre E.P.
      • Rodriguez-Claro M.L.
      • Rico-Villademoros F.
      • Vilchez J.S.
      • Hidalgo J.
      • Delgado-Rodriguez A.
      Effects of pool-based exercise in fibromyalgia symptomatology and sleep quality: a prospective randomised comparison between stretching and Ai Chi.
      • Demir-Gocmen D.
      • Altan L.
      • Korkmaz N.
      • Arabaci R.
      Effect of supervised exercise program including balance exercises on the balance status and clinical signs in patients with fibromyalgia.
      • Fernandes G.
      • Jennings F.
      • Nery Cabral M.V.
      • Pirozzi Buosi A.L.
      • Natour J.
      Swimming improves pain and functional capacity of patients with fibromyalgia: a randomized controlled trial.
      • Collado-Mateo D.
      • Dominguez-Munoz F.J.
      • Adsuar J.C.
      • Garcia-Gordillo M.A.
      • Gusi N.
      Effects of exergames on quality of life, pain, and disease effect in women with fibromyalgia: a randomized controlled trial.
      • Gavi M.B.R.O.
      • Vassalo D.V.
      • Amaral F.T.
      • et al.
      Strengthening exercises improve symptoms and quality of life but do not change autonomic modulation in fibromyalgia: a randomized clinical trial.
      • Jentoft E.S.
      • Kvalvik A.G.
      • Mengshoel M.
      Effects of pool-based and land-based aerobic exercise on women with fibromyalgia/chronic widespread muscle pain.
      • Jones K.D.
      • Burckhardt C.S.
      • Clark S.R.
      • Bennett R.M.
      • Potempa K.M.
      A randomized controlled trial of muscle strengthening versus flexibility training in fibromyalgia.
      • Kendall S.A.
      • Brolin-Magnusson K.
      • Soren B.
      • Gerdle B.
      • Henriksson K.G.
      A pilot study of body awareness programs in the treatment of fibromyalgia syndrome.
      • López-Pousa S.
      • Bassets Pagès G.
      • Monserrat-Vila S.
      • de Gracia Blanco M.
      • Hidalgo Colomé J.
      • Garre-Olmo J.
      Sense of well-being in patients with fibromyalgia: aerobic exercise program in a mature forest-a pilot study.
      • Lopez-Rodriguez M.M.
      • Fernandez-Martinez M.
      • Mataran-Penarrocha G.A.
      • Rodriguez-Ferrer M.E.
      • Granados Gamez G.
      • Aguilar Ferrandiz E.
      [Effectiveness of aquatic biodance on sleep quality, anxiety and other symptoms in patients with fibromyalgia] [Spanish].
      • Mannerkorpi K.
      • Nordeman L.
      • Cider Å.
      • Jonsson G.
      Does moderate-to-high intensity Nordic walking improve functional capacity and pain in fibromyalgia? A prospective randomized controlled trial.
      • Norregaard J.
      • Lykkegaard J.J.
      • Mehlsen J.
      • DanneskioldSamsoe B.
      Exercise training in treatment of fibromyalgia.
      • van Santen M.
      • Bolwijn P.
      • Landewe R.
      • Verstappen F.
      • Bakker C.
      • Hidding A.
      • et al.
      High or low intensity aerobic fitness training in fibromyalgia: does it matter?.
      • Vitorino D.F.D.
      • Carvalho L.B.C.
      • do Prado G.F.
      Hydrotherapy and conventional physiotherapy improve total sleep time and quality of life of fibromyalgia patients: randomized clinical trial.
      • Etnier J.L.
      • Karper W.B.
      • Gapin J.I.
      • Barella L.A.
      • Chang Y.K.
      • Murphy K.J.
      Exercise, fibromyalgia, and fibrofog: a pilot study.
      • Wang C.
      • Schmid C.H.
      • Rones R.
      • et al.
      A randomized trial of tai chi for fibromyalgia.
      • Wang C.
      • Schmid C.H.
      • Fielding R.A.
      • et al.
      Effect of tai chi versus aerobic exercise for fibromyalgia: comparative effectiveness randomized controlled trial.
      • Genc A.
      • Tur B.S.
      • Aytur Y.K.
      • Oztuna D.
      • Erdogan M.F.
      Does aerobic exercise affect the hypothalamic-pituitary-adrenal hormonal response in patients with fibromyalgia syndrome?.
      • Assumpcao A.
      • Matsutani L.A.
      • Yuan S.L.
      • Santo A.S.
      • Sauer J.
      • Mango P.
      • et al.
      Muscle stretching exercises and resistance training in fibromyalgia: which is better? A three-arm randomized controlled trial.
      • McBeth J.
      • Prescott G.
      • Scotland G.
      • Lovell K.
      • Keeley P.
      • Hannaford P.
      • et al.
      Cognitive behavior therapy, exercise, or both for treating chronic widespread pain.
      • Schachter C.L.
      • Busch A.J.
      • Peloso P.M.
      • Sheppard M.S.
      Effects of short versus long bouts of aerobic exercise in sedentary women with fibromyalgia: a randomized controlled trial.
      • da Silva M.M.
      • Albertini R.
      • de Tarso Camillo de Carvalho P.
      • et al.
      Randomized, blinded, controlled trial on effectiveness of photobiomodulation therapy and exercise training in the fibromyalgia treatment.
      • Giannotti E.
      • Koutsikos K.
      • Pigatto M.
      • Rampudda M.E.
      • Doria A.
      • Masiero S.
      Medium-/long-term effects of a specific exercise protocol combined with patient education on spine mobility, chronic fatigue, pain, aerobic fitness and level of disability in fibromyalgia.
      • Haak T.
      • Scott B.
      The effect of Qigong on fibromyalgia (FMS): a controlled randomized study.
      • Hakkinen A.
      • Hakkinen K.
      • Hannonen P.
      • Alen M.
      Strength training induced adaptations in neuromuscular function of premenopausal women with fibromyalgia: comparison with healthy women.
      • Lynch M.
      • Sawynok J.
      • Hiew C.
      • Marcon D.
      A randomized controlled trial of qigong for fibromyalgia.
      • Mannerkorpi K.
      • Nyberg B.
      • Ahlmen M.
      • Ekdahl C.
      Pool exercise combined with an education program for patients with fibromyalgia syndrome. A prospective, randomized study.
      • Sanudo B.
      • Carrasco L.
      • de Hoyo M.
      • Figueroa A.
      • Saxton J.M.
      Vagal modulation and symptomatology following a 6-month aerobic exercise program for women with fibromyalgia.
      Of them, 4 studies included 3 arms (ie, control group and 2 exercise intervention groups, each with a different exercise training such as aerobic in 1 group and flexibility in another group) and therefore they were included for addressing both aims of the present review.
      • Assumpcao A.
      • Matsutani L.A.
      • Yuan S.L.
      • Santo A.S.
      • Sauer J.
      • Mango P.
      • et al.
      Muscle stretching exercises and resistance training in fibromyalgia: which is better? A three-arm randomized controlled trial.
      • McBeth J.
      • Prescott G.
      • Scotland G.
      • Lovell K.
      • Keeley P.
      • Hannaford P.
      • et al.
      Cognitive behavior therapy, exercise, or both for treating chronic widespread pain.
      • Schachter C.L.
      • Busch A.J.
      • Peloso P.M.
      • Sheppard M.S.
      Effects of short versus long bouts of aerobic exercise in sedentary women with fibromyalgia: a randomized controlled trial.
      • da Silva M.M.
      • Albertini R.
      • de Tarso Camillo de Carvalho P.
      • et al.
      Randomized, blinded, controlled trial on effectiveness of photobiomodulation therapy and exercise training in the fibromyalgia treatment.
      Thus, a total 20 RCTs
      • Alentorn-Geli E.
      • Padilla J.
      • Moras G.
      • Lazaro Haro C.
      • Fernandez-Sola J.
      Six weeks of whole-body vibration exercise improves pain and fatigue in women with fibromyalgia.
      • Carson J.W.
      • Carson K.M.
      • Jones K.D.
      • Bennett R.M.
      • Wright C.L.
      • Mist S.D.
      A pilot randomized controlled trial of the Yoga of Awareness program in the management of fibromyalgia.
      • Tomas-Carus P.
      • Gusi N.
      • Hakkinen A.
      • Hakkinen 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.
      • Tomas-Carus P.
      • Hakkinen A.
      • Gusi N.
      • Leal A.
      • Hakkinen K.
      • Ortega-Alonso A.
      Aquatic training and detraining on fitness and quality of life in fibromyalgia.
      • Valkeinen H.
      • Alen M.
      • Hakkinen A.
      • Hannonen P.
      • Kukkonen-Harjula K.
      • Hakkinen K.
      Effects of concurrent strength and endurance training on physical fitness and symptoms in postmenopausal women with fibromyalgia: a randomized controlled trial.
      • van Santen M.
      • Bolwijn P.
      • Verstappen F.
      • et al.
      A randomized clinical trial comparing fitness and biofeedback training versus basic treatment in patients with fibromyalgia.
      • Wigers S.H.
      • Stiles T.C.
      • Vogel P.A.
      Effects of aerobic exercise versus stress management treatment in fibromyalgia. A 4.5 year prospective study.
      • Wong A.
      • Figueroa A.
      • Sanchez-Gonzalez M.A.
      • Son W.-M.
      • Chernykh O.
      • Park S.-Y.
      Effectiveness of tai chi on cardiac autonomic function and symptomatology in women with fibromyalgia: a randomized controlled trial.
      ,
      • Collado-Mateo D.
      • Dominguez-Munoz F.J.
      • Adsuar J.C.
      • Garcia-Gordillo M.A.
      • Gusi N.
      Effects of exergames on quality of life, pain, and disease effect in women with fibromyalgia: a randomized controlled trial.
      ,
      • Etnier J.L.
      • Karper W.B.
      • Gapin J.I.
      • Barella L.A.
      • Chang Y.K.
      • Murphy K.J.
      Exercise, fibromyalgia, and fibrofog: a pilot study.
      ,
      • Assumpcao A.
      • Matsutani L.A.
      • Yuan S.L.
      • Santo A.S.
      • Sauer J.
      • Mango P.
      • et al.
      Muscle stretching exercises and resistance training in fibromyalgia: which is better? A three-arm randomized controlled trial.
      • McBeth J.
      • Prescott G.
      • Scotland G.
      • Lovell K.
      • Keeley P.
      • Hannaford P.
      • et al.
      Cognitive behavior therapy, exercise, or both for treating chronic widespread pain.
      • Schachter C.L.
      • Busch A.J.
      • Peloso P.M.
      • Sheppard M.S.
      Effects of short versus long bouts of aerobic exercise in sedentary women with fibromyalgia: a randomized controlled trial.
      • da Silva M.M.
      • Albertini R.
      • de Tarso Camillo de Carvalho P.
      • et al.
      Randomized, blinded, controlled trial on effectiveness of photobiomodulation therapy and exercise training in the fibromyalgia treatment.
      • Giannotti E.
      • Koutsikos K.
      • Pigatto M.
      • Rampudda M.E.
      • Doria A.
      • Masiero S.
      Medium-/long-term effects of a specific exercise protocol combined with patient education on spine mobility, chronic fatigue, pain, aerobic fitness and level of disability in fibromyalgia.
      • Haak T.
      • Scott B.
      The effect of Qigong on fibromyalgia (FMS): a controlled randomized study.
      • Hakkinen A.
      • Hakkinen K.
      • Hannonen P.
      • Alen M.
      Strength training induced adaptations in neuromuscular function of premenopausal women with fibromyalgia: comparison with healthy women.
      • Lynch M.
      • Sawynok J.
      • Hiew C.
      • Marcon D.
      A randomized controlled trial of qigong for fibromyalgia.
      • Mannerkorpi K.
      • Nyberg B.
      • Ahlmen M.
      • Ekdahl C.
      Pool exercise combined with an education program for patients with fibromyalgia syndrome. A prospective, randomized study.
      • Sanudo B.
      • Carrasco L.
      • de Hoyo M.
      • Figueroa A.
      • Saxton J.M.
      Vagal modulation and symptomatology following a 6-month aerobic exercise program for women with fibromyalgia.
      and 21 RTs
      • Bircan C.
      • Karasel S.A.
      • Akgun B.
      • El O.
      • Alper S.
      Effects of muscle strengthening versus aerobic exercise program in fibromyalgia.
      • Calandre E.P.
      • Rodriguez-Claro M.L.
      • Rico-Villademoros F.
      • Vilchez J.S.
      • Hidalgo J.
      • Delgado-Rodriguez A.
      Effects of pool-based exercise in fibromyalgia symptomatology and sleep quality: a prospective randomised comparison between stretching and Ai Chi.
      • Demir-Gocmen D.
      • Altan L.
      • Korkmaz N.
      • Arabaci R.
      Effect of supervised exercise program including balance exercises on the balance status and clinical signs in patients with fibromyalgia.
      • Fernandes G.
      • Jennings F.
      • Nery Cabral M.V.
      • Pirozzi Buosi A.L.
      • Natour J.
      Swimming improves pain and functional capacity of patients with fibromyalgia: a randomized controlled trial.
      ,
      • Gavi M.B.R.O.
      • Vassalo D.V.
      • Amaral F.T.
      • et al.
      Strengthening exercises improve symptoms and quality of life but do not change autonomic modulation in fibromyalgia: a randomized clinical trial.
      • Jentoft E.S.
      • Kvalvik A.G.
      • Mengshoel M.
      Effects of pool-based and land-based aerobic exercise on women with fibromyalgia/chronic widespread muscle pain.
      • Jones K.D.
      • Burckhardt C.S.
      • Clark S.R.
      • Bennett R.M.
      • Potempa K.M.
      A randomized controlled trial of muscle strengthening versus flexibility training in fibromyalgia.
      • Kendall S.A.
      • Brolin-Magnusson K.
      • Soren B.
      • Gerdle B.
      • Henriksson K.G.
      A pilot study of body awareness programs in the treatment of fibromyalgia syndrome.
      • López-Pousa S.
      • Bassets Pagès G.
      • Monserrat-Vila S.
      • de Gracia Blanco M.
      • Hidalgo Colomé J.
      • Garre-Olmo J.
      Sense of well-being in patients with fibromyalgia: aerobic exercise program in a mature forest-a pilot study.
      • Lopez-Rodriguez M.M.
      • Fernandez-Martinez M.
      • Mataran-Penarrocha G.A.
      • Rodriguez-Ferrer M.E.
      • Granados Gamez G.
      • Aguilar Ferrandiz E.
      [Effectiveness of aquatic biodance on sleep quality, anxiety and other symptoms in patients with fibromyalgia] [Spanish].
      • Mannerkorpi K.
      • Nordeman L.
      • Cider Å.
      • Jonsson G.
      Does moderate-to-high intensity Nordic walking improve functional capacity and pain in fibromyalgia? A prospective randomized controlled trial.
      • Norregaard J.
      • Lykkegaard J.J.
      • Mehlsen J.
      • DanneskioldSamsoe B.
      Exercise training in treatment of fibromyalgia.
      • van Santen M.
      • Bolwijn P.
      • Landewe R.
      • Verstappen F.
      • Bakker C.
      • Hidding A.
      • et al.
      High or low intensity aerobic fitness training in fibromyalgia: does it matter?.
      • Vitorino D.F.D.
      • Carvalho L.B.C.
      • do Prado G.F.
      Hydrotherapy and conventional physiotherapy improve total sleep time and quality of life of fibromyalgia patients: randomized clinical trial.
      ,
      • Wang C.
      • Schmid C.H.
      • Rones R.
      • et al.
      A randomized trial of tai chi for fibromyalgia.
      • Wang C.
      • Schmid C.H.
      • Fielding R.A.
      • et al.
      Effect of tai chi versus aerobic exercise for fibromyalgia: comparative effectiveness randomized controlled trial.
      • Genc A.
      • Tur B.S.
      • Aytur Y.K.
      • Oztuna D.
      • Erdogan M.F.
      Does aerobic exercise affect the hypothalamic-pituitary-adrenal hormonal response in patients with fibromyalgia syndrome?.
      • Assumpcao A.
      • Matsutani L.A.
      • Yuan S.L.
      • Santo A.S.
      • Sauer J.
      • Mango P.
      • et al.
      Muscle stretching exercises and resistance training in fibromyalgia: which is better? A three-arm randomized controlled trial.
      • McBeth J.
      • Prescott G.
      • Scotland G.
      • Lovell K.
      • Keeley P.
      • Hannaford P.
      • et al.
      Cognitive behavior therapy, exercise, or both for treating chronic widespread pain.
      • Schachter C.L.
      • Busch A.J.
      • Peloso P.M.
      • Sheppard M.S.
      Effects of short versus long bouts of aerobic exercise in sedentary women with fibromyalgia: a randomized controlled trial.
      • da Silva M.M.
      • Albertini R.
      • de Tarso Camillo de Carvalho P.
      • et al.
      Randomized, blinded, controlled trial on effectiveness of photobiomodulation therapy and exercise training in the fibromyalgia treatment.
      were included in the review. Figure 1 shows a PRISMA diagram.
      Figure thumbnail gr1
      Fig 1Flow chart showing the results of the selection process. Four studies included a usual care (control) group and 2 different exercise interventions. Thus, they were included in the analyses related to the primary and second aims of the present review.
      Of the 20 RCTs that compared the effectiveness of exercise versus usual care, 9 included both outcomes of interest,
      • Carson J.W.
      • Carson K.M.
      • Jones K.D.
      • Bennett R.M.
      • Wright C.L.
      • Mist S.D.
      A pilot randomized controlled trial of the Yoga of Awareness program in the management of fibromyalgia.
      ,
      • Tomas-Carus P.
      • Hakkinen A.
      • Gusi N.
      • Leal A.
      • Hakkinen K.
      • Ortega-Alonso A.
      Aquatic training and detraining on fitness and quality of life in fibromyalgia.
      ,
      • Valkeinen H.
      • Alen M.
      • Hakkinen A.
      • Hannonen P.
      • Kukkonen-Harjula K.
      • Hakkinen K.
      Effects of concurrent strength and endurance training on physical fitness and symptoms in postmenopausal women with fibromyalgia: a randomized controlled trial.
      ,
      • Wigers S.H.
      • Stiles T.C.
      • Vogel P.A.
      Effects of aerobic exercise versus stress management treatment in fibromyalgia. A 4.5 year prospective study.
      ,
      • Wong A.
      • Figueroa A.
      • Sanchez-Gonzalez M.A.
      • Son W.-M.
      • Chernykh O.
      • Park S.-Y.
      Effectiveness of tai chi on cardiac autonomic function and symptomatology in women with fibromyalgia: a randomized controlled trial.
      ,
      • McBeth J.
      • Prescott G.
      • Scotland G.
      • Lovell K.
      • Keeley P.
      • Hannaford P.
      • et al.
      Cognitive behavior therapy, exercise, or both for treating chronic widespread pain.
      ,
      • da Silva M.M.
      • Albertini R.
      • de Tarso Camillo de Carvalho P.
      • et al.
      Randomized, blinded, controlled trial on effectiveness of photobiomodulation therapy and exercise training in the fibromyalgia treatment.
      ,
      • Giannotti E.
      • Koutsikos K.
      • Pigatto M.
      • Rampudda M.E.
      • Doria A.
      • Masiero S.
      Medium-/long-term effects of a specific exercise protocol combined with patient education on spine mobility, chronic fatigue, pain, aerobic fitness and level of disability in fibromyalgia.
      ,
      • Hakkinen A.
      • Hakkinen K.
      • Hannonen P.
      • Alen M.
      Strength training induced adaptations in neuromuscular function of premenopausal women with fibromyalgia: comparison with healthy women.
      8 included only fatigue,
      • Alentorn-Geli E.
      • Padilla J.
      • Moras G.
      • Lazaro Haro C.
      • Fernandez-Sola J.
      Six weeks of whole-body vibration exercise improves pain and fatigue in women with fibromyalgia.
      ,
      • Tomas-Carus P.
      • Gusi N.
      • Hakkinen A.
      • Hakkinen 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.
      ,
      • van Santen M.
      • Bolwijn P.
      • Verstappen F.
      • et al.
      A randomized clinical trial comparing fitness and biofeedback training versus basic treatment in patients with fibromyalgia.
      ,
      • Collado-Mateo D.
      • Dominguez-Munoz F.J.
      • Adsuar J.C.
      • Garcia-Gordillo M.A.
      • Gusi N.
      Effects of exergames on quality of life, pain, and disease effect in women with fibromyalgia: a randomized controlled trial.
      ,
      • Etnier J.L.
      • Karper W.B.
      • Gapin J.I.
      • Barella L.A.
      • Chang Y.K.
      • Murphy K.J.
      Exercise, fibromyalgia, and fibrofog: a pilot study.
      ,
      • Assumpcao A.
      • Matsutani L.A.
      • Yuan S.L.
      • Santo A.S.
      • Sauer J.
      • Mango P.
      • et al.
      Muscle stretching exercises and resistance training in fibromyalgia: which is better? A three-arm randomized controlled trial.
      ,
      • Schachter C.L.
      • Busch A.J.
      • Peloso P.M.
      • Sheppard M.S.
      Effects of short versus long bouts of aerobic exercise in sedentary women with fibromyalgia: a randomized controlled trial.
      ,
      • Palstam A.
      • Mannerkorpi K.
      Work ability in fibromyalgia: an update in the 21st century.
      and 3 included only sleep quality.
      • Haak T.
      • Scott B.
      The effect of Qigong on fibromyalgia (FMS): a controlled randomized study.
      ,
      • Lynch M.
      • Sawynok J.
      • Hiew C.
      • Marcon D.
      A randomized controlled trial of qigong for fibromyalgia.
      ,
      • Sanudo B.
      • Carrasco L.
      • de Hoyo M.
      • Figueroa A.
      • Saxton J.M.
      Vagal modulation and symptomatology following a 6-month aerobic exercise program for women with fibromyalgia.
      Of the 21 RTs that compared the effectiveness of different exercise interventions, 12 included both outcomes of interest,
      • Bircan C.
      • Karasel S.A.
      • Akgun B.
      • El O.
      • Alper S.
      Effects of muscle strengthening versus aerobic exercise program in fibromyalgia.
      • Calandre E.P.
      • Rodriguez-Claro M.L.
      • Rico-Villademoros F.
      • Vilchez J.S.
      • Hidalgo J.
      • Delgado-Rodriguez A.
      Effects of pool-based exercise in fibromyalgia symptomatology and sleep quality: a prospective randomised comparison between stretching and Ai Chi.
      • Demir-Gocmen D.
      • Altan L.
      • Korkmaz N.
      • Arabaci R.
      Effect of supervised exercise program including balance exercises on the balance status and clinical signs in patients with fibromyalgia.
      ,
      • Jentoft E.S.
      • Kvalvik A.G.
      • Mengshoel M.
      Effects of pool-based and land-based aerobic exercise on women with fibromyalgia/chronic widespread muscle pain.
      ,
      • Jones K.D.
      • Burckhardt C.S.
      • Clark S.R.
      • Bennett R.M.
      • Potempa K.M.
      A randomized controlled trial of muscle strengthening versus flexibility training in fibromyalgia.
      ,
      • López-Pousa S.
      • Bassets Pagès G.
      • Monserrat-Vila S.
      • de Gracia Blanco M.
      • Hidalgo Colomé J.
      • Garre-Olmo J.
      Sense of well-being in patients with fibromyalgia: aerobic exercise program in a mature forest-a pilot study.
      ,
      • Lopez-Rodriguez M.M.
      • Fernandez-Martinez M.
      • Mataran-Penarrocha G.A.
      • Rodriguez-Ferrer M.E.
      • Granados Gamez G.
      • Aguilar Ferrandiz E.
      [Effectiveness of aquatic biodance on sleep quality, anxiety and other symptoms in patients with fibromyalgia] [Spanish].
      ,
      • Norregaard J.
      • Lykkegaard J.J.
      • Mehlsen J.
      • DanneskioldSamsoe B.
      Exercise training in treatment of fibromyalgia.
      ,
      • Wang C.
      • Schmid C.H.
      • Rones R.
      • et al.
      A randomized trial of tai chi for fibromyalgia.
      ,
      • Genc A.
      • Tur B.S.
      • Aytur Y.K.
      • Oztuna D.
      • Erdogan M.F.
      Does aerobic exercise affect the hypothalamic-pituitary-adrenal hormonal response in patients with fibromyalgia syndrome?.
      ,
      • McBeth J.
      • Prescott G.
      • Scotland G.
      • Lovell K.
      • Keeley P.
      • Hannaford P.
      • et al.
      Cognitive behavior therapy, exercise, or both for treating chronic widespread pain.
      ,
      • da Silva M.M.
      • Albertini R.
      • de Tarso Camillo de Carvalho P.
      • et al.
      Randomized, blinded, controlled trial on effectiveness of photobiomodulation therapy and exercise training in the fibromyalgia treatment.
      7 included only fatigue,
      • Fernandes G.
      • Jennings F.
      • Nery Cabral M.V.
      • Pirozzi Buosi A.L.
      • Natour J.
      Swimming improves pain and functional capacity of patients with fibromyalgia: a randomized controlled trial.
      ,
      • Gavi M.B.R.O.
      • Vassalo D.V.
      • Amaral F.T.
      • et al.
      Strengthening exercises improve symptoms and quality of life but do not change autonomic modulation in fibromyalgia: a randomized clinical trial.
      ,
      • Kendall S.A.
      • Brolin-Magnusson K.
      • Soren B.
      • Gerdle B.
      • Henriksson K.G.
      A pilot study of body awareness programs in the treatment of fibromyalgia syndrome.
      ,
      • Mannerkorpi K.
      • Nordeman L.
      • Cider Å.
      • Jonsson G.
      Does moderate-to-high intensity Nordic walking improve functional capacity and pain in fibromyalgia? A prospective randomized controlled trial.
      ,
      • Vitorino D.F.D.
      • Carvalho L.B.C.
      • do Prado G.F.
      Hydrotherapy and conventional physiotherapy improve total sleep time and quality of life of fibromyalgia patients: randomized clinical trial.
      ,
      • Assumpcao A.
      • Matsutani L.A.
      • Yuan S.L.
      • Santo A.S.
      • Sauer J.
      • Mango P.
      • et al.
      Muscle stretching exercises and resistance training in fibromyalgia: which is better? A three-arm randomized controlled trial.
      ,
      • Schachter C.L.
      • Busch A.J.
      • Peloso P.M.
      • Sheppard M.S.
      Effects of short versus long bouts of aerobic exercise in sedentary women with fibromyalgia: a randomized controlled trial.
      and 2 included only sleep quality.
      • van Santen M.
      • Bolwijn P.
      • Landewe R.
      • Verstappen F.
      • Bakker C.
      • Hidding A.
      • et al.
      High or low intensity aerobic fitness training in fibromyalgia: does it matter?.
      ,
      • Wang C.
      • Schmid C.H.
      • Fielding R.A.
      • et al.
      Effect of tai chi versus aerobic exercise for fibromyalgia: comparative effectiveness randomized controlled trial.
      A summary of the characteristics of the RCTs and RTs included in the present review is presented in supplemental tables S1 and S2 (available online only at http://www.archives-pmr.org/), respectively.
      A moderate risk of bias was present in most of the included RCTs and RTs (see supplemental figs S1 and S2 for overall summaries and supplemental figs S3 and S4 [available online only at http://www.archives-pmr.org/] for specific information on each individual included work per study design). No study reported having conflicts of interest.

      Synthesis of the data

      Figure 2 presents a meta-analysis conducted in 1003 people with fibromyalgia (61% randomly allocated into exercise interventions). In comparison with usual care, exercise interventions were effective for reducing fatigue in fibromyalgia (pooled SMD, –0.47; 95% CI, –0.67 to –0.27). This finding was robust across 2 sensitivity analyses, as shown in supplemental figures S5 and S6 (available online only at http://www.archives-pmr.org/): (1) when a study with high risk of bias
      • Assumpcao A.
      • Matsutani L.A.
      • Yuan S.L.
      • Santo A.S.
      • Sauer J.
      • Mango P.
      • et al.
      Muscle stretching exercises and resistance training in fibromyalgia: which is better? A three-arm randomized controlled trial.
      was not included in the meta-analysis (pooled SMD, –0.49; 95% CI, –0.71 to –0.27) and (2) when fixed effects models were computed (pooled SMD, –0.40; 95% CI, –0.53 to –0.26). Supplemental figure S7 (available online only at http://www.archives-pmr.org/) demonstrates the funnel plot, which did not indicate publication bias.
      Figure thumbnail gr2
      Fig 2Pooled effects of randomized controlled trials analyzing the effectiveness of exercise in reducing fatigue in people with fibromyalgia. Analyses were conducted using a random effects model. A, aerobic exercise; CI, confidence interval; Co-edu, cointervention-education; Co-photo, cointervention-phototherapy; df, degrees of freedom; F, flexibility exercise; IV, inverse variance; L-B, land-based exercise; M, meditative exercise; R, resistance exercise; Std, standardized; TC, tai chi; W-B, water-based exercise; Y, yoga.
      Owing to the high heterogeneity (ie, I2=51%) observed across RCTs testing the effects of exercise on fatigue, we explored several post hoc analyses. Most of them were not significant, as the effects on fatigue were similar between levels of adherence: (1) studies in which participants had to attend to at least 80% of the training sessions (ie, adherence) to be included in the analyses and those studies with a lower or no adherence criterion, (2) sex of participants: studies in which only women participated versus those in which both sexes were included, (3) type of intervention: only exercise versus cointerventions, (4) type of exercise: meditative exercise programs (ie, tai chi, yoga, qigong) versus others (ie, aerobic, muscular resistance, flexibility), (5) sample size: those with at least 20 participants in each group versus others, (6) type of setting in which exercise was performed: land-based versus water-based, and (7) training intensity: low-to-moderate versus moderate-to-high. Supplemental figures S8 to S14 (available online only at http://www.archives-pmr.org/) show these non-significant findings. Interestingly, those studies in which fatigue was the primary outcome (fig 3) and used a shorter (<24wk) non-aerobic exercise intervention resulted in greater effect on fatigue (greater effect sizes) than comparative studies (supplemental figs S15 and S16; available online only at http://www.archives-pmr.org/).
      Figure thumbnail gr3
      Fig 3Post hoc analysis showing the pooled effects of randomized trials analyzing the effectiveness of studies in which fatigue was the primary outcome versus the remaining studies for lowering fatigue in people with fibromyalgia. Analyses were conducted using a random effects model.
      Figure 4 depicts a meta-analysis conducted in 731 people with fibromyalgia (59% randomly allocated into exercise interventions). In comparison with usual care, exercise interventions had a small effect on enhancing sleep quality in fibromyalgia (pooled SMD, –0.17; 95% CI, –0.32 to –0.01). This finding was robust across 2 sensitivity analyses, as shown in supplemental figures S17 and S18 (available online only at http://www.archives-pmr.org/): (1) when a study with high risk of bias
      • Haak T.
      • Scott B.
      The effect of Qigong on fibromyalgia (FMS): a controlled randomized study.
      was not included in the meta-analysis (pooled SMD, –0.19; 95% CI, –0.35 to –0.02), and (2) when fixed effects model were computed (pooled SMD, –0.17; 95% CI, –0.32 to –0.02). Owing to the small heterogeneity (ie, I2=5%), post hoc analyses were not needed. Supplemental figure S19 (available online only at http://www.archives-pmr.org/) depicts the funnel plot, which did not indicate publication bias.
      Figure thumbnail gr4
      Fig 4Pooled effects of randomized controlled trials analyzing the effectiveness of exercise in enhancing sleep quality in people with fibromyalgia. Analyses were conducted using a random effects model.
      Table 1 shows that when comparing exercise versus usual care, there was low to moderate quality evidence for the beneficial effects of exercise on fatigue, whereas the evidence was moderate for benefits on sleep quality.
      Table 1Level of quality evidence for the effectiveness of exercise for reducing fatigue and enhancing sleep quality in fibromyalgia
      Certainty AssessmentNo. of ParticipantsEffectCertaintyDirection
      No. of StudiesStudy DesignRisk of BiasInconsistencyIndirectnessImprecisionPublication BiasExerciseUsual CareSMD (95% CI)Size
      Outcome: fatigue
      17Randomized controlled trialsNot seriousSeriousNot seriousUnclearNot serious612/1003 (62%)391/1003 (39%)–0.47 (–0.67 to –0.27)Moderate⨁⨁◯◯ to ⨁⨁⨁◯

      Low to moderate
      In favor of exercise
      Outcome: sleep quality
      12Randomized controlled trialsNot seriousNot seriousNot seriousSeriousNot serious431/731 (59%)300/731 (41%)–0.17 (–0.32 to –0.01)Small⨁⨁⨁◯

      Moderate
      In favor of exercise
      In the 21 RTs included in the present review, a wide range of exercise interventions were implemented and compared in a total of 1254 individuals with fibromyalgia who were randomly allocated into different interventions. Thus, it was difficult to perform robust comparisons. However, we were able to quantify 1 comparison for sleep quality and 3 for fatigue. First, when comparing different types of exercise, meditative exercise programs were more effective for improving sleep quality but not for lowering fatigue (fig 5; [pooled SMD, –0.80; 95% CI, –1.57 to –0.02] and supplemental fig S20, available online only at http://www.archives-pmr.org/ [pooled SMD, –0.39; 95% CI, –0.88 to 0.11]). Second, the effectiveness of resistance versus flexibility training was similar for fatigue (supplemental fig S21, available online only at http://www.archives-pmr.org/ [pooled SMD, –1.64; 95% CI, –4.31 to 1.02]). Third, the effectiveness of water- versus land-based exercise was also similar for fatigue (supplemental figure S22, available online only at http://www.archives-pmr.org/ [pooled SMD, 0.00; 95% CI, –0.42 to 0.43]).
      Figure thumbnail gr5
      Fig 5Post hoc analysis showing the pooled effects of randomized trials analyzing the effectiveness of meditative exercise vs the remaining types of exercise for enhancing sleep quality in people with fibromyalgia. Analyses were conducted using a random effects model.

      Discussion

      This systematic review aimed to determine the effectiveness of exercise on fatigue and sleep quality in those with fibromyalgia and to identify which type of exercise interventions might be the most effective in achieving these outcomes. In the current review, we found that, compared with usual care, exercise has moderate effects for lowering fatigue and small effects for improving sleep quality. We also observed that, compared with other types of exercise, meditative exercise programs were more effective for improving sleep quality but not for lowering fatigue. In interpreting the findings of this review, several factors must be noted. First, most of the studies were based on aerobic exercise. Thus, the effect sizes of the present meta-analyses may more accurately reflect the effectiveness of aerobic training on fatigue and sleep quality than the effects of other types of exercise. Indeed, we observed that those exercise interventions that did not include aerobic exercise appeared to be more effective at reducing fatigue. Second, the effects of exercise on fatigue were highly variable across studies (I2=51%) and remarkably higher when fatigue was the main outcome. Third, there was a lack of high-quality studies in the field and, consequently, the quality of evidence provided in the present review is low to moderate for the effectiveness of exercise in reducing fatigue (the evidence is in favor of exercise but the effect size is unclear and likely to be moderate) and moderate for small effects of exercise (of any type) on enhancing sleep quality.

      Effectiveness of exercise for reducing fatigue in fibromyalgia

      Owing to the limited number of studies included in previous meta-analyses, their findings were inconclusive and inconsistent. For example, Busch et al meta-analyzed 2 resistance training studies (n=81) showing significant pooled reductions on fatigue (P<.001).
      • Busch A.J.
      • Webber S.C.
      • Richards R.S.
      • et al.
      Resistance exercise training for fibromyalgia.
      However, Bidonde et al recently meta-analyzed 4 aerobic exercise studies (n=286)
      • Bidonde J.
      • Busch A.J.
      • Schachter C.L.
      • et al.
      Aerobic exercise training for adults with fibromyalgia.
      in which the P value of the pooled effects for the exercise group was 0.06. Recently, Bidonde et al meta-analyzed a sample size of 493 adults with fibromyalgia, estimating that the effects of mixed exercise training (ie, 2 or more types of exercise combined) on fatigue were significant (P<.001).
      • Bidonde J.
      • Busch A.J.
      • Schachter C.L.
      • et al.
      Mixed exercise training for adults with fibromyalgia.
      Using similar statistical methods to previous meta-analyses but in a larger sample size (n=1003), our pooled estimation showed that exercise produces significant and probably meaningful (moderate effect size) reduction in fatigue in fibromyalgia. Thus, the comprehensive approach followed in the present meta-analysis allowed us to robustly determine, for the first time, the overall effects of exercise on fatigue in large sample of individuals with fibromyalgia.

      Effectiveness of exercise for improving sleep quality in fibromyalgia

      Previous meta-analyses were unable to determine the effectiveness of exercise on sleep quality in fibromyalgia owing to the paucity of research. Indeed, most failed to find RCTs on this topic. Given the extent of sleep dysfunction in individuals with fibromyalgia, it is important to determine the effectiveness of exercise for improving sleep quality in this population. The most comprehensive review to date included only 2 studies examining sleep and reported moderate effects of exercise for enhancing sleep quality (n=104).
      • Bidonde J.
      • Busch A.J.
      • Webber S.C.
      • et al.
      Aquatic exercise training for fibromyalgia.
      The number of included studies in the present work was considerably higher (13 RCTs, n=806), allowing us to better estimate the effectiveness of exercise for improving sleep quality in fibromyalgia. The effectiveness of exercise (of any type) in enhancing sleep quality in fibromyalgia was limited (small effect). However, meditative exercise programs (ie, tai chi, yoga, qigong) may offer a promising approach. Although there are potential mechanisms that can provide a rationale to support the effectiveness of meditative exercise on improving sleep quality, our finding is based on an imprecise estimation (SMD, –0.80; 95% CI, –1.57 to –0.02) from a relatively small sample size (141 participants in meditative exercise vs 177 participants in other types of exercise). Thus, further high-quality experimental research is required to confirm or refute our findings.

      Exercise mechanisms for fatigue and sleep quality in fibromyalgia

      Aberrations in the central nervous system are well-known in fibromyalgia.
      • Wood P.B.
      • Ledbetter C.R.
      • Glabus M.F.
      • Broadwell L.K.
      • Patterson J.C.
      Hippocampal metabolite abnormalities in fibromyalgia: correlation with clinical features.
      • McCrae C.
      • O’Shea A.
      • Boissoneault J.
      • et al.
      Fibromyalgia patients have reduced hippocampal volume compared with healthy controls.
      • González-Roldán A.M.
      • Bomba I.C.
      • Diesch E.
      • Montoya P.
      • Flor H.
      • Kamping S.
      Controllability and hippocampal activation during pain expectation in fibromyalgia syndrome.
      For example, compared with nonfibromyalgia controls, abnormal levels of metabolites (eg, reductions in the ratio of N-acetylaspartate to creatine) have been observed in the hippocampus of people with fibromyalgia,
      • Wood P.B.
      • Ledbetter C.R.
      • Glabus M.F.
      • Broadwell L.K.
      • Patterson J.C.
      Hippocampal metabolite abnormalities in fibromyalgia: correlation with clinical features.
      as well as structural abnormalities (eg, lower volume)
      • McCrae C.
      • O’Shea A.
      • Boissoneault J.
      • et al.
      Fibromyalgia patients have reduced hippocampal volume compared with healthy controls.
      and functional changes (eg, increased activation).
      • González-Roldán A.M.
      • Bomba I.C.
      • Diesch E.
      • Montoya P.
      • Flor H.
      • Kamping S.
      Controllability and hippocampal activation during pain expectation in fibromyalgia syndrome.
      Another system that might be altered in fibromyalgia is the hypothalamic-pituitary-adrenal axis, as well as a sympathetic hyperactivity mediated by a dysfunction in the autonomic nervous system.
      • Martinez-Lavin M.
      Biology and therapy of fibromyalgia. Stress, the stress response system, and fibromyalgia.
      These alterations may be related to increased levels of fatigue.
      • Wood P.B.
      • Ledbetter C.R.
      • Glabus M.F.
      • Broadwell L.K.
      • Patterson J.C.
      Hippocampal metabolite abnormalities in fibromyalgia: correlation with clinical features.
      Interestingly, exercise may revert these aberrations by regulating the levels of metabolites and promoting angiogenesis, neurogenesis, and connectivity of the hippocampus.
      • Valim V.
      • Natour J.
      • Xiao Y.
      • et al.
      Effects of physical exercise on serum levels of serotonin and its metabolite in fibromyalgia: a randomized pilot study.
      ,
      • Hillman C.H.
      • Erickson K.I.
      • Kramer A.F.
      Be smart, exercise your heart: exercise effects on brain and cognition.
      The present meta-analyses demonstrated that exercise had a small beneficial effect on sleep quality in fibromyalgia. In this disease, hyperactivity of the sympathetic nervous system is well-documented and, thus, stress levels are considerably high.
      • Petzke F.
      • Clauw D.J.
      Sympathetic nervous system function in fibromyalgia.
      ,
      • Sarzi-Puttini P.
      • Atzeni F.
      • Diana A.
      • Doria A.
      • Furlan R.
      Increased neural sympathetic activation in fibromyalgia syndrome.
      Physiological responses to exercise often include a decrease in this sympathetic tone and a shift toward parasympathetic activity, which may be related to muscular and nervous relaxation, leading to reductions in stress levels and, finally, to improvement in sleep quality.
      • O’Connor P.J.
      • Youngstedt S.D.
      Influence of exercise on human sleep.
      • Kubitz K.A.
      • Landers D.M.
      • Petruzzello S.J.
      • Han M.
      The effects of acute and chronic exercise on sleep. A meta-analytic review.
      • Stults-Kolehmainen M.A.
      • Sinha R.
      The effects of stress on physical activity and exercise.
      In this respect, our review showed that meditative exercise programs were more effective in improving sleep quality than other types of exercise. Although meditative exercise is safe in fibromyalgia, little is known about their mechanisms of action. It is likely that this type of exercise can enhance the parasympathetic activity and reduce sympathetic tone by decreasing activation of the hypothalamic-pituitary-adrenal axis. Moreover, meditative exercise may facilitate enhanced rapid eye movement sleep by increasing central nervous system inhibitory c-aminobutyric acid and serotonin levels.
      • Karimi M.
      • Yazdani Noori A.
      Serotonin and mood state changes in response to a period of yoga training in well-trained wrestlers.

      Clinical applications

      The recent European League Against Rheumatism recommendations for the management of fibromyalgia highlight exercise as the only therapy with a strong level of evidence.
      • Macfarlane G.J.
      • Kronisch C.
      • Dean L.E.
      • et al.
      EULAR revised recommendations for the management of fibromyalgia.
      These recommendations were based on the findings provided by systematic review of previous reviews. As we have discussed, although previous systematic reviews showed reliable findings for pain management, they have provided limited evidence on the effectiveness of exercise for reducing fatigue and increasing sleep quality in fibromyalgia.
      • Bidonde J.
      • Busch A.J.
      • Schachter C.L.
      • et al.
      Aerobic exercise training for adults with fibromyalgia.
      ,
      • Busch A.J.
      • Webber S.C.
      • Richards R.S.
      • et al.
      Resistance exercise training for fibromyalgia.
      The present meta-analyses suggest that the effectiveness of exercise may differ for different outcomes. This means that it cannot be assumed that the benefits of exercise for pain automatically extend to other symptoms of the condition. An interesting finding for health care providers has emerged from our review in that fatigue reductions were higher when the main outcome of the study was fatigue. Therefore, instead of designing a “fix-all” exercise protocol for fibromyalgia, exercise programs should be designed as outcome-specific by considering how fibromyalgia manifests in the person who is going to engage in the program. For example, meditative exercise programs (eg, tai chi or qigong) may be more advisable for people with fibromyalgia who experience difficulty sleeping.
      The studies included in the present systematic review investigated a wide range of exercise programs, including different types of exercise, intensities, frequencies, and program durations. Although we explored several post hoc analyses, we were unable to determine the most effective exercise intervention for reducing fatigue. From our approach to subgrouping the effects of different exercise interventions compared with usual care, we observed that the ideal intervention for reducing fatigue in fibromyalgia appears to be specifically designed for such an outcome, lasts less than 24 weeks, and does not involve aerobic exercise. Collectively, the high heterogeneity that emerged from the effects of exercise on fatigue limits the establishment of evidence-based guidelines. Although the American College of Sports Medicine has released specific recommendations to consider when conducting exercise interventions in fibromyalgia,
      • Pescatello L.S.
      American College of Sports Medicine
      ACSM’s guidelines for exercise testing and prescription. 9th ed.
      a recent review has reported poor therapeutic validity of studies that accomplish these American College of Sports Medicine exercise recommendations.
      • Álvarez-Gallardo I.C.
      • Bidonde J.
      • Busch A.
      • et al.
      Therapeutic validity of exercise interventions in the management of fibromyalgia.
      Standard exercise interventions for the average or most common profile of people with fibromyalgia appears misjudged as people with fibromyalgia are heterogeneous.
      • Estévez-López F.
      • Segura-Jiménez V.
      • Álvarez-Gallardo I.C.
      • et al.
      Adaptation profiles comprising objective and subjective measures in fibromyalgia: the al-Ándalus project.
      Thus, personalized exercise programs are warranted. In this context, some people with fibromyalgia may experience fears related to engaging in exercise
      • Russell D.
      • Álvarez Gallardo I.C.
      • Wilson I.
      • et al.
      “Exercise to me is a scary word”: perceptions of fatigue, sleep dysfunction, and exercise in people with fibromyalgia syndrome-a focus group study.
      or a discordance of being more capable to engage in exercise than is self-perceived.
      • Estévez-López F.
      • Álvarez-Gallardo I.C.
      • Segura-Jiménez V.
      • et al.
      The discordance between subjectively and objectively measured physical function in women with fibromyalgia: association with catastrophizing and self-efficacy cognitions. The al-Ándalus project.
      Individuals with these characteristics may be more likely to experience exercise as stressful. Therefore, exercise interventions should not only be tailored to how fibromyalgia manifests in each person but also to (more) general characteristics of the person.

      Implications for research agenda

      Findings of the present study provide evidence indicating that exercise is effective for reducing fatigue in fibromyalgia. However, future research is needed to determine what type of exercise is most beneficial for people with fibromyalgia, which intensity is best, the optimal length of the training, and the most beneficial delivery method. Our findings indicate that exercise appears to promote only small benefits on sleep quality in fibromyalgia. Although relaxation is a potential mechanism by which exercise might improve sleep quality, not all types of exercise promote relaxation. Thus, meditative exercise programs that suppose a lower physical load than other types of exercises could be more effective for enhancing sleep quality in fibromyalgia. Therefore, large, high-quality experimental studies testing the effectiveness of very gentle exercise specifically designed for enhancing sleep quality in fibromyalgia are warranted in the future. In addition, further research testing the effectiveness of exercise in objectively measured fatigue or sleep quality is warranted.

      Study limitations

      The most common limitations among the included studies were as follows: (1) the long-term effects of the interventions were not reported; (2) results were not stratified by sex, and most of the participants were women. Moreover, we did not include conference proceedings and other types of gray literature owing to the often low quality of reporting in conference abstracts.

      Conclusions

      We provided low-to-moderate quality evidence that exercise is moderately effective for lowering fatigue and demonstrated that there is moderate evidence of small effects of exercise for enhancing sleep quality in fibromyalgia. Although speculative, meditative exercise programs may be a promising approach for improving sleep quality in fibromyalgia. As most of the interventions involved aerobic exercise, research using other types of exercise is warranted. Instead of designing “fix-all” and “one size fits all” protocols, exercise programs should be specifically designed for the outcome that is targeted and tailored to the characteristics of the person who is going to engage in the exercise in order to be as effective as possible.

      Supplier

      • a.
        Review Manager version 5.3; Cochrane Collaboration.

      Supplementary Data

      Figure thumbnail figs1
      Supplemental Fig S1Summary of risk of bias of the randomized controlled trials testing the effectiveness of exercise interventions in comparison to usual care.
      Figure thumbnail figs2
      Supplemental Fig S2Summary of risk of bias of the randomized trials comparing the effectiveness of different exercise interventions.
      Figure thumbnail figs3
      Supplemental Fig S3Risk of bias of each randomized controlled trial testing the effectiveness of exercise interventions in comparison to usual care.
      Figure thumbnail figs4
      Supplemental Fig S4Risk of bias of each randomized trial comparing the effectiveness of different exercise interventions.
      Figure thumbnail figs5
      Supplemental Fig S5Pooled effects of the randomized controlled trials analyzing the effectiveness of exercise in reducing fatigue in people with fibromyalgia: sensitivity analyses excluding studies with high risk of bias.
      Figure thumbnail figs6
      Supplemental Fig S6Pooled effects of the randomized controlled trials analyzing the effectiveness of exercise in reducing fatigue in people with fibromyalgia: sensitivity analyses using fixed effects model.
      Figure thumbnail figs7
      Supplemental Fig S7Funnel plot of the randomized controlled trials analyzing the effectiveness of exercise in reducing fatigue in people with fibromyalgia.
      Figure thumbnail figs8
      Supplemental Fig S8Post hoc analyses of the randomized controlled trials testing the effectiveness of exercise interventions in fatigue in comparison to usual care: subgroups according to levels of adherence (80% adherence at minimum vs lower rates or none adherence criterion).
      Figure thumbnail figs9
      Supplemental Fig S9Post hoc analyses of the randomized controlled trials testing the effectiveness of exercise interventions in fatigue in comparison to usual care: gender of the participants (only women vs both genders).
      Figure thumbnail figs10
      Supplemental Fig S10Post hoc analyses of the randomized controlled trials testing the effectiveness of exercise interventions in fatigue in comparison to usual care: subgroups according to type of interventions (only exercise vs exercise + cointervention),
      Figure thumbnail figs11
      Supplemental Fig S11Post hoc analyses of the randomized controlled trials testing the effectiveness of exercise interventions in fatigue in comparison to usual care: subgroups according to type of exercise (meditative exercise vs other types).
      Figure thumbnail figs12
      Supplemental Fig S12Post hoc analyses of the randomized controlled trials testing the effectiveness of exercise interventions in fatigue in comparison to usual care: subgroups according to sample size (20 participants per group at minimum vs lower sample sizes).
      Figure thumbnail figs13
      Supplemental Fig S13Post hoc analyses of the randomized controlled trials testing the effectiveness of exercise interventions in fatigue in comparison to usual care: subgroups according to settings (land-based vs water-based exercise).
      Figure thumbnail figs14
      Supplemental Fig S14Post hoc analyses of the randomized controlled trials testing the effectiveness of exercise interventions in fatigue in comparison to usual care: subgroups according to intensity (low-to-moderate vs moderate-to-high).
      Figure thumbnail figs15
      Supplemental Fig S15Post hoc analyses of the randomized controlled trials testing the effectiveness of exercise interventions in fatigue in comparison to usual care: subgroups according to aerobic exercise (aerobic exercise in insolation or combined with other exercises vs other exercises that did not include aerobic training).
      Figure thumbnail figs16
      Supplemental Fig S16Post hoc analyses of the randomized controlled trials testing the effectiveness of exercise interventions in fatigue in comparison to usual care: subgroups according to length of the intervention (24 weeks at minimum vs shorter interventions).
      Figure thumbnail figs17
      Supplemental Fig S17Pooled effects of the randomized controlled trials analyzing the effectiveness of exercise in enhancing sleep quality in people with fibromyalgia: sensitivity analyses excluding studies with high risk of bias.
      Figure thumbnail figs18
      Supplemental Fig S18Pooled effects of the randomized controlled trials analyzing the effectiveness of exercise in enhancing sleep quality in people with fibromyalgia: sensitivity analyses using fixed effects model.
      Figure thumbnail figs19
      Supplemental Fig S19Funnel plot of the randomized controlled trials analyzing the effectiveness of exercise in enhancing sleep quality in people with fibromyalgia.
      Figure thumbnail figs20
      Supplemental Fig S20Pooled effects of the randomized trials comparing the effectiveness of meditative exercise and other types of exercise in fatigue in people with fibromyalgia.
      Figure thumbnail figs21
      Supplemental Fig S21Pooled effects of the randomized trials comparing the effectiveness of resistance and flexibility exercise in fatigue in people with fibromyalgia.
      Figure thumbnail figs22
      Supplemental Fig S22Pooled effects of the randomized trials comparing the effectiveness of land-based and water-based exercise in fatigue in people with fibromyalgia.

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