Fphys 14 1170621

TYPE Systematic Review
PUBLISHED 12 April 2023

DOI 10.3389/fphys.2023.1170621
Optimal dose and type of exercise

OPEN ACCESS to reduce pain, anxiety and
EDITED BY
Luis Carrasco,
Sevilla University, Spain
increase quality of life in patients
REVIEWED BY
J. Derek Kingsley,
with fibromyalgia. A systematic
Kent State University, United States
David Varillas-Delgado,
Universidad Francisco de Vitoria, Spain
review with meta-analysis
*CORRESPONDENCE
Esteban Obrero-Gaitán, Daniel Rodríguez-Almagro 1, María Del Moral-García 2,
[email protected]
María del Carmen López-Ruiz 2, Irene Cortés-Pérez 2,
SPECIALTY SECTION
This article was submitted
Esteban Obrero-Gaitán 2* and Rafael Lomas-Vega 2
to Exercise Physiology, 1
Department of Nursing, Physiotherapy and Medicine, University of Almería, Almería, Spain, 2Department
a section of the journal of Health Sciences, University of Jaén, Jaén, Spain
Frontiers in Physiology
RECEIVED 22 February 2023

ACCEPTED 28 March 2023
PUBLISHED 12 April 2023
The aim of our meta-analysis was to compile the available evidence to evaluate the
CITATION
Rodríguez-Almagro D,
effect of physical exercise-based therapy (PEBT) on pain, impact of the disease,
Del Moral-García M, López-Ruiz MdC, quality of life (QoL) and anxiety in patients with fibromyalgia syndrome (FMS), to
Cortés-Pérez I, Obrero-Gaitán E and determine the effect of different modes of physical exercise-based therapy, and the
Lomas-Vega R (2023), Optimal dose and
type of exercise to reduce pain, anxiety
most effective dose of physical exercise-based therapy for improving each outcome.
and increase quality of life in patients with A systematic review and meta-analysis was carried out. The PubMed (MEDLINE),
fibromyalgia. A systematic review SCOPUS, Web of Science, CINAHL Complete and Physiotherapy Evidence Database
with meta-analysis.
Front. Physiol. 14:1170621.
(PEDro) databases were searched up to November 2022. Randomized controlled
doi: 10.3389/fphys.2023.1170621 trials (RCTs) comparing the effects of physical exercise-based therapy and other
COPYRIGHT
treatments on pain, the impact of the disease, QoL and/or anxiety in patients with FMS
© 2023 Rodríguez-Almagro, Del Moral- were included. The standardized mean difference (SMD) and a 95% CI were estimated
García, López-Ruiz, Cortés-Pérez, for all the outcome measures using random effect models. Three reviewers
Obrero-Gaitán and Lomas-Vega. This is
an open-access article distributed under independently extracted data and assessed the risk of bias using the PEDro scale.
the terms of the Creative Commons Sixty-eight RCTs involving 5,474 participants were included. Selection, detection and
Attribution License (CC BY). The use, performance biases were the most identified. In comparison to other therapies, at
distribution or reproduction in other
forums is permitted, provided the original immediate assessment, physical exercise-based therapy was effective at improving
author(s) and the copyright owner(s) are pain [SMD-0.62 (95%CI, −0.78 to −0.46)], the impact of the disease [SMD-0.52 (95%
credited and that the original publication CI, −0.67 to −0.36)], the physical [SMD 0.51 (95%CI, 0.33 to 0.69)] and mental
in this journal is cited, in accordance with
accepted academic practice. No use, dimensions of QoL [SMD 0.48 (95%CI, 0.29 to 0.67)], and the anxiety [SMD-0.36
distribution or reproduction is permitted (95%CI, −0.49 to −0.25)]. The most effective dose of physical exercise-based therapy
which does not comply with these terms. for reducing pain was 21–40 sessions [SMD-0.83 (95%CI, 1.1–−0.56)], 3 sessions/
week [SMD-0.82 (95%CI, −1.2–−0.48)] and 61–90 min per session [SMD-1.08 (95%
CI, −1.55–−0.62)]. The effect of PEBT on pain reduction was maintained up to
12 weeks [SMD-0.74 (95%CI, −1.03–−0.45)]. Among patients with FMS, PEBT
(including circuit-based exercises or exercise movement techniques) is effective at
reducing pain, the impact of the disease and anxiety as well as increasing QoL.
Systematic Review Registration: PROSPERO https://www.crd.york.ac.uk/
PROSPERO/, identifier CRD42021232013.
KEYWORDS
fibromyalgia, exercise therapy, pain, quality of life, anxiety, women, disability,

recommended dose
Frontiers in Physiology 01 frontiersin.org

Rodríguez-Almagro et al. 10.3389/fphys.2023.1170621
1 Introduction large variety of aerobic, resistance, strength, balance, and

proprioceptive exercises that can help to reduce pain and muscle
Fibromyalgia syndrome (FMS) is a chronic musculoskeletal debility in these patients and could increase their QoL. Some of the
disorder mainly characterized by impaired pain processing, resulting main advantages of PEBT are that it is an active and ludic therapy
in generalized, diffuse and non-inflammatory pain in different body that can be performed in groups and that can increase social support
localizations (Galvez-Sánchez and Reyes del Paso, 2020; Sarzi-Puttini between patients with FMS. Pilates (Franco et al., 2023), dance
et al., 2020). In addition to pain, other disabling symptoms of FMS (Murillo-Garcia et al., 2022), yoga (Allsop et al., 2022), tai chi
include movement restrictions, fatigue (Gota, 2022), balance disorders (Cheng et al., 2019), circuit training (aerobic, strength and
(Peinado-Rubia et al., 2020; Núñez-Fuentes et al., 2021), mood disorders multicomponent) (Vilarino et al., 2021; Araya-Quintanilla et al.,
[such as anxiety, depression or low self-esteem (Galvez-Sánchez et al., 2022; Estrada-Marcén et al., 2023), body awareness therapy (Bravo
2019)], sleep disorders (Frange et al., 2014) and sexual dysfunctions et al., 2019), and videogames (Cortés-Pérez et al., 2021) are the most
(Ricoy-Cano et al., 2021). FMS is a highly prevalent disorder–it affects common forms to peform PEBT in patients with FMS; the effects of
approximately 2.4% of the world’s population (Queiroz, 2013). these forms of therapy have been widely assessed in the scientific
Moreover, it has been found to be more common among women literature, and promising results have been obtained.
(the ratio of women to men is 3:1) and middle-aged people In recent years, some reviews have assessed the effect of different
(approximately 30–50 years of age (Queiroz, 2013; Häuser et al., types of PEBT to improve more common symptoms in FMS. An
2015)). FMS causes a high socioeconomic burden on the healthcare interesting and common finding in these reviews is that patients
system (Skaer, 2014). It is estimated to cost €7256–7900 per patient each undergoing PEBT do not report adverse events, thus indicating that
year in developed countries; furthermore, it leads to high rates of PEBT is a safe therapy to use in FMS (Bidonde et al., 2014a).
absenteeism, unemployment, and early retirement as well as a higher Although the results presented in these works generally support the
number of days off work (Schaefer et al., 2011). These costs are mainly use of PEBT, they are difficult to synthesize, as each review assessed
due to medical visits, specialized consultations, diagnostic tests, one specific type of PEBT, such as Tai Chi (Cheng et al., 2019),
medicines and complementary therapies to provide psychological flexibility exercise training (Kim et al., 2019), aquatic exercise
support (Feliu-Soler et al., 2016). (Bidonde et al., 2014b) or exergames using virtual reality devices
Despite the prevalence of this health problem, its causes are still (Cortés-Pérez et al., 2021). In addition, other reviews assessed
unknown, and the pathophysiology of FMS is not entirely clear different exercise approaches, but the number of studies included
(Schmidt-Wilcke and Diers, 2017). Early etiological theories were was low, making it difficult to generalize the findings (Sosa-Reina
mainly based on psychogenic factors, as no physical signs were et al., 2017; Del-Moral-García et al., 2020; Estévez-López et al.,
found to justify the pain in these patients (Bair and Krebs, 2020). 2021). To date, there have been no comprehensive reviews that
Over time, advances in research have cast doubt on these assess the effect of different PEBT modalities and provide evidence
hypotheses, suggesting that FMS may be caused by a process of about the correct doses for patients with FMS. Therefore, the
central sensitization and a mismatch in pain processing (Staud et al., primary objective of this systematic review and meta-analysis was
2007; Goubert et al., 2017; Bair and Krebs, 2020; Oliva et al., 2022). to compile all the available evidence to assess the effect of PEBT on
Various neuroimaging tests have revealed alterations in the central pain, disability impact, QoL and anxiety in patients with FMS. As a
nervous system (CNS), such as morphological changes in the brain secondary objective, we aimed to determine the appropriate dose of
regions in charge of processing nociceptive stimuli, an increase in PEBT to improve each outcome in FMS patients. Finally, we aimed
nervous activity in these areas and an imbalance in the to assess the effect of PEBT according to specific modalities of PEBT
concentration of related neurotransmitters (Giesecke et al., 2004; (circuit-based exercise or exercise-movement techniques).
Napadow and Harris, 2014; Schmidt-Wilcke and Diers, 2017; Bair
and Krebs, 2020), which could lead to an exacerbation of painful
sensations and a decrease in endogenous pain inhibition systems 2 Methods
(O’Brien et al., 2018; Bair and Krebs, 2020). Although the specific
cause of FMS is not yet known, numerous risk factors have been 2.1 Protocol and registration
identified, such as previous medical pathologies, poor quality of life
(QoL), sedentary lifestyle, depression, hypochondria, childhood The current systematic review and meta-analysis was conducted
problems or history of abuse (Creed, 2020). in accordance with the Preferred Reporting Items for Systematic
Due to the considerable heterogeneity of FMS symptomatology, Reviews and Meta-Analysis (PRISMA 2020 statement) (Page et al.,
there is no single treatment for all patients (Häuser et al., 2015). 2021) and the Cochrane Handbook for Systematic Reviews of
According to a meta-analysis by Nüesch et al., 2013, FMS requires Interventions (Higgins and Thomas, 2020). In addition, the
multidisciplinary management that includes both pharmacological protocol of this review was previously registered in the
and non-pharmacological measures (Nüesch et al., 2013). The International Prospective Register of Systematic Reviews
measures applied should mainly focus on symptom management (PROSPERO: CRD42021232013).
and increasing functionality and QoL (Bair and Krebs, 2020).
According to the latest guidelines proposed by the European
League against Rheumatism (EULAR) for the management of 2.2 Literature search strategy
FMS, the therapeutic pillars should be cognitive behavioral
therapy and graded and paced physical exercise (Macfarlane Two authors, independently, searched the PubMed
et al., 2017). Physical exercise-based therapy (PEBT) includes a (MEDLINE), Scopus, Web of Science (WOS), CINAHL Complete

and Physiotherapy Evidence Database (PEDro) databases up to (mean and standard deviation). If the means and standard
November 2022. Additional sources were searched, including deviations were not available, other types of statistical data
previously published reviews, gray literature and expert (median, standard error or interquartile range) were collected so
documents. Boolean operators were used in the search and we do that they could be transformed and subsequently included in the
not use restrictions related with publication date and language. All current meta-analysis (Hozo et al., 2005; Higgins and Thomas,
searches were supervised by a third author who is an expert in 2020).
bibliographic searches. The following Medical Subject Headings
(MeSH) terms were used to search the PubMed (MEDLINE)
database: (fatigue syndrome, chronic[mh] OR fatigue syndrome, 2.5 Variables
chronic[tiab] OR fibromyalgia[mh] OR fibromyalgia[tiab]) AND
(exercise[mh] OR exercise[tiab] OR exercise therapy[mh] OR The outcomes examined in this systematic review and meta-analysis
exercise therapy[tiab] OR physical exercise[tiab] OR physical were as follows: pain, the impact of FMS, QoL (physical and mental
activity[tiab] OR training[tiab]) AND (randomized controlled trial dimension), and anxiety experienced in patients with FMS. To assess
[publication type] OR randomized controlled trial[tiab] OR clinical these variables, we included quantitative data from validated tests that
trial[publication type] OR clinical trial[tiab] OR controlled clinical measure the same construct. So, for pain, we would include data from the
trial[publication type] OR controlled clinical trial[tiab]) NOT Visual Analogue Scale (VAS), the Numeric Pain Rating Scale (NPRS) or
(systematic review[publication type] OR systematic review[tiab] pain dimension of the Fibromyalgia Impact Questionnaire (FIQ), among
OR meta-analysis[publication type] OR meta-analysis[tiab] OR others. For impact of FMS, we would include studies that assessed it with
review[publication type] OR review[tiab]). This search strategy FIQ; for QoL, questionnaires or scales that assessed it, such as SF-36 or
was adapted to the other databases (Supplementary Table S1). EuroQoL-5D; and finally, for anxiety, questionnaires such as Beck
Anxiety Inventory (BAI) or Hospital Anxiety and Depression
Inventory (HADS), can be selected.
2.3 Inclusion and exclusion criteria
In accordance with the PICO framework, the inclusion criteria 2.6 Quality assessment
were as follows: 1) Population, patients diagnosed with FMS; 2)
Intervention, PEBT; 3) Comparison, interventions other from The PEDro scale was used to assess the methodological quality and
PEBT, including usual care; and 4) Outcomes, pain, the impact risk of bias of the studies included in the review. This scale is composed
of FMS, anxiety and physical/mental QoL. Additionally, we included of 11 items that can be scored as “yes” (if the criteria are met) or “no” (if
randomized controlled trials (RCTs) and pilot RCTs that provided the criteria are not met) (Macedo et al., 2010). The total score ranged
post-intervention quantitative data (n, mean and standard deviation from 0 (very low methodological quality and high risk of bias) to 10 (high
of each group) of the outcomes of interest, thus enabling us to methodological quality and very low risk of bias). The PEDro scale
perform meta-analysis. The exclusion criteria were 1) studies whose categorizes methodological quality as “excellent” (10–9 points), “good”
population did not comprise exclusively FMS patients and 2) studies (eight to six points), “fair” (five to four points), and “poor” (3 points or
that reported quantitative data that were not suitable for meta- less) (Cashin and McAuley, 2020).
analysis. To assess the quality of evidence in each meta-analysis, we used the
Grading of Recommendations Assessment, Development, and Evaluation
(GRADE) (Atkins et al., 2004). The quality of evidence is determined
2.4 Data extraction based on the following items: risk of bias in each study, inconsistency,
indirect evidence, imprecision and risk of publication bias. All these items,
Two authors, independently, analyzed the titles and abstracts of except the risk of bias, were assessed using the GRADE checklist of
each reference retrieved. If a study was selected by one of the Meader (Meader et al., 2014). Two authors, independently, participated in
authors, it was examined in detail to determine its inclusion or these assessments, and doubts were resolved by a third author.
exclusion and the corresponding reasons for extracting the data of
interest for meta-analysis. Disagreements between the two reviewers
were resolved by consulting a third reviewer. The data extracted of 2.7 Statistical analysis
the articles selected were collected in a standardized form in
Microsoft Excel. A third author was consulted in case of Statistical analysis was performed with Comprehensive Meta-
disagreements. The following data were extracted from each Analysis version 3.0 (Biostat, Englewood, NJ, United States) by
study: authorship and publication data, country and total sample two authors. Meta-analysis was only performed if at least two
size. From each group, we collected sample size, age (mean or range), studies reported data for an outcome. The DerSimonian and
body mass index (BMI) and gender. From the experimental Laird random effects analysis was employed (DerSimonian and
intervention (PEBT) groups, we extracted the type of PEBT Laird, 1986), and the effect size was calculated using Cohen’s
(exercise-based circuit or exercise movement techniques) and the standardized mean difference (SMD) and its 95% CI (Cohen J,
protocol of application (weeks, sessions per week and minutes per 1977). Cohen’s SMD can be categorized into four levels: no effect
session). From the comparison intervention groups, we extracted the (SMD = 0), small (SMD = 0.2), medium (SMD = 0.5) and large
type of intervention. Finally, regarding the outcomes of interest, we (SMD >0.8) (Faraone, 2008). In addition, when an outcome was
extracted the test employed in each study and the quantitative data assessed with the same test, the mean difference (MD) between

groups was calculated to compare our results with the minimum

clinically important difference (MCID) for the test. The results of
each meta-analysis were shown in forest plots (Rücker and
Schwarzer, 2020), and the risk of publication bias was assessed
via visual analysis of the forest plot (a symmetric plot indicates a
low risk of publication bias, and an asymmetric plot indicated a
high risk of publication bias) (Sterne and Egger, 2001) and with
Egger’s test (p < 0.1 indicates possible risk of publication) (Egger
et al., 1997). Furthermore, the trim-and-fill calculation was used
to estimate the adjusted SMD, taking into account any possible
risk of publication bias (Duval and Tweedie, 2000). In accordance
with Rothman’s recommendations for the effect size variation
limit in the assessment of confounding bias, when the adjusted
SMD varied by more than 10% from the original, raw pooled
effect, the level of quality of evidence lowered by one level, even if
the funnel plot was only slightly asymmetric (Rothman et al.,
2008). Finally, the heterogeneity was assessed with the Q-test (p <
0.1 indicates risk of heterogeneity) and the degree of
inconsistency (I2) (I2 <25% indicates low heterogeneity; I2
between 25%–50% indicates moderate heterogeneity, and
I2 >50% indicates high heterogeneity) (Higgins et al., 2002;
Higgins et al., 2003).
The contribution of each study to the overall pooled effect was
assessed via sensitivity analysis using the leave-one-out method
(Higgins and Thomas, 2020). In addition, multiple subgroup FIGURE 1
analyses were performed. First, a subgroup analysis was PRISMA Flow Diagram from selection of the studies.
performed based on the specific PEBT modality employed:
circuit-based exercise (aerobic, strength, flexibility, endurance
exercises) versus other therapies, and exercise-movement
techniques (Tai Chi, yoga, Pilates) versus other therapies. A Carus et al., 2018; Tomas-Carus et al., 2021; Günendi et al., 2008;
second subgroup analysis was performed based on the follow-up Carson et al., 2010; Fontaine et al., 2010; Sañudo Corrales et al.,
duration: immediate (just after completion of therapy), short-term 2010; Arcos-Carmona et al., 2011; Núñez et al., 2011; Sañudo
(12 weeks), medium-term (24 weeks) and long-term (48 weeks). In et al., 2011; Sañudo et al., 2015; Baptista et al., 2012; García-
addition, to determine the optimal dose of PEBT for improvement of Martínez et al., 2012; Jones et al., 2012; Kayo et al., 2012; Castel
each outcome, subgroup analyses were performed based on 1) the et al., 2013; Chan et al., 2014; Chan et al., 2017; Clarke-Jenssen
number of sessions (4–20, 21–40, 41–60 and more than 60 sessions); et al., 2014; Giannotti et al., 2014; Martín et al., 2014; Larsson
2) the number of sessions per week (1, 2, 3, 4 and 5 days per week); et al., 2015; Latorre Román et al., 2015; Ericsson et al., 2016;
and 3) the duration of each session (0–30, 31–60, 61–90 and Espí-López et al., 2016; Kurt, 2016; Maddali Bongi et al., 2016;
90–120 min). Ekici et al., 2017; Windthorst et al., 2017; Assumpção et al., 2018;
Kashikar-Zuck et al., 2018; Wong et al., 2018; Andrade et al.,
2019; Silva et al., 2019; Atan and Karavelioğlu, 2020; Garrido-
3 Results Ardila et al., 2020; Izquierdo-Alventosa et al., 2020; Izquierdo-
Alventosa et al., 2020; Sauch Valmaña et al., 2020; Serrat et al.,
3.1 Study selection 2020; Serrat et al., 2021b; Serrat et al., 2021a; Serrat et al., 2022;
Fonseca et al., 2021; Haugmark et al., 2021; Hernando-Garijo
The initial searches identified 2,620 cites and 1,426 were et al., 2021; Arroyo-Fernández et al., 2022; de Lorena et al.,
screened by title/abstract after to remove duplicate studies. Nine 2022). The literature searches and study selection process is
hundred forty-two were excluded for not being relevant and shown in the PRISMA flowchart (Figure 1), which shows the
416 did not meet the inclusion criteria. Ultimately, 68 studies number of excluded references together with the reasons.
were included in this systematic review with meta-analysis
(Wigers et al., 1996; Mannerkorpi et al., 2000; Mannerkorpi
et al., 2009; Gowans et al., 2001; King et al., 2002; Richards, 2002; 3.2 Characteristics of the studies included in
Astin et al., 2003; Schachter et al., 2003; Cedraschi, 2004; the review
Redondo et al., 2004; Sencan et al., 2004; Da Costa et al.,
2005; Kingsley et al., 2005; Zijlstra, 2005; Gusi et al., 2006; Sixty-eight RCTs were included (Wigers et al., 1996;
Hammond and Freeman, 2006; Fontaine and Haaz, 2007; Mannerkorpi et al., 2000; Mannerkorpi et al., 2009; Gowans
Munguía-Izquierdo and Legaz-Arrese, 2007; Rooks, 2007; et al., 2001; King et al., 2002; Richards, 2002; Astin et al., 2003;
Tomas-Carus et al., 2007; Tomas-Carus et al., 2009; Tomas- Schachter et al., 2003; Cedraschi, 2004; Redondo et al., 2004; Sencan

et al., 2004; Da Costa et al., 2005; Kingsley et al., 2005; Zijlstra, 2005; Garrido-Ardila et al., 2020; Izquierdo-Alventosa et al., 2020;
Gusi et al., 2006; Hammond and Freeman, 2006; Fontaine and Haaz, Izquierdo-Alventosa et al., 2021; Serrat et al., 2020; Serrat et al.,
2007; Munguía-Izquierdo and Legaz-Arrese, 2007; Rooks, 2007; 2021b; Serrat et al., 2021a; Serrat et al., 2022; Fonseca et al., 2021;
Tomas-Carus et al., 2007; Tomas-Carus et al., 2009; Tomas- Haugmark et al., 2021; Hernando-Garijo et al., 2021; de Lorena et al.,
Carus et al., 2018; Tomas-Carus et al., 2021; Günendi et al., 2022), 19 studies (27.9%) presented fair quality (Mannerkorpi et al.,
2008; Carson et al., 2010; Fontaine et al., 2010; Sañudo Corrales 2000; Richards, 2002; Astin et al., 2003; Cedraschi, 2004; Zijlstra,
et al., 2010; Arcos-Carmona et al., 2011; Núñez et al., 2011; Sañudo 2005; Gusi et al., 2006; Fontaine and Haaz, 2007; Tomas-Carus et al.,
et al., 2011; Sañudo et al., 2015; Baptista et al., 2012; García-Martínez 2007; Fontaine et al., 2010; Arcos-Carmona et al., 2011; García-
et al., 2012; Jones et al., 2012; Kayo et al., 2012; Castel et al., 2013; Martínez et al., 2012; Giannotti et al., 2014; Martín et al., 2014;
Chan et al., 2014; Chan et al., 2014; Clarke-Jenssen et al., 2014; Latorre Román et al., 2015; Maddali Bongi et al., 2016; Ekici et al.,
Giannotti et al., 2014; Martín et al., 2014; Larsson et al., 2015; Latorre 2017; Windthorst et al., 2017; Assumpção et al., 2018; Sauch
Román et al., 2015; Ericsson et al., 2016; Espí-López et al., 2016; Valmaña et al., 2020), and only 1 study (1.4%) presented poor
Kurt, 2016; Maddali Bongi et al., 2016; Ekici et al., 2017; Windthorst Quality (Sencan et al., 2004). Items 5 and 6 of the PEDro scale were
et al., 2017; Assumpção et al., 2018; Kashikar-Zuck et al., 2018; not met in any study, and the majority of studies showed a risk of
Wong et al., 2018; Andrade et al., 2019; Silva et al., 2019; Atan and performance bias. Assessors were not blinded in the majority of the
Karavelioğlu, 2020; Garrido-Ardila et al., 2020; Izquierdo-Alventosa studies, and thus, there was a risk of detection bias. Finally, some
et al., 2020; Izquierdo-Alventosa et al., 2021; Sauch Valmaña et al., studies did not meet Item 3, indicating a possible risk of selection
2020; Serrat et al., 2020; Serrat et al., 2021b; Serrat et al., 2021a; Serrat bias. Table 1 shows the PEDro score of each included study.
et al., 2022; Fonseca et al., 2021; Haugmark et al., 2021; Hernando-
Garijo et al., 2021; Arroyo-Fernández et al., 2022; de Lorena et al.,
2022) and reported data from 5,474 patients with FMS. The mean 3.4 Synthesis of variables
age was 49.23 ± 5.57 years. A total of 93% of the patients were
female, and the mean body mass index (BMI) was 27.4 ± 2.39 kg/m2. The studies included provided data for each variable thorough
Data on PEBT were reported from 2,893 patients with FMS (48.06 ± the following questionnaires or measures. Pain was assessed with
5.21 years and 27.53 ± 2.38 kg/m2), such as circuit-based exercises or data from the VAS, the NPRS, the Brief Pain Inventory (BPI), the
exercise-movement techniques. The duration of the proposed FIQ-pain dimension and the Pain Catastrophizing Scale (PCS). The
interventions in each study ranged from 2 to 32 weeks. The impact of FMS was assessed with data from the FIQ. QoL was
control groups consisted of 2,581 participants with FMS with a assessed using data from the SF-36. Anxiety was analyzed using data
mean age of 48.91 ± 5.90 years and a mean BMI of 27.34 ± 2.67 kg/ from the BAI, the State Trait Anxiety Inventory (STAI), the
m2. These individuals underwent non-PEBT interventions, such as Psychological General Wellbeing (PGWB), the HADS-anxiety
usual care, educational therapy, relaxation therapy, magnetotherapy, dimension, the Arthritis Impact Measurement Scales (AIMS), the
electrotherapy, psychology, balneotherapy or pharmacotherapy. All VAS for anxiety, and the FIQ-anxiety dimension.
studies included in this review were RCTs and assessed at least one
of the main outcomes (i.e., pain, the impact of FMS, QoL and
anxiety). This meta-analysis includes assessments conducted just 3.5 Effects of PEBT on pain
after the intervention (immediate effect) and during follow-up (12,
24 and 48 weeks). Supplementary Table S4 showed the main Forty-seven studies (Wigers et al., 1996; Mannerkorpi et al.,
characteristics of the included studies. 2000; Mannerkorpi et al., 2009; Schachter et al., 2003; Cedraschi,
2004; Redondo et al., 2004; Sencan et al., 2004; Zijlstra, 2005; Gusi
et al., 2006; Hammond and Freeman, 2006; Fontaine and Haaz,
3.3 Methodological quality and risk of bias 2007; Munguía-Izquierdo and Legaz-Arrese, 2007; Rooks, 2007;
Günendi et al., 2008; Carson et al., 2010; Fontaine et al., 2010;
The mean methodological quality of the studies included was Baptista et al., 2012; Jones et al., 2012; Kayo et al., 2012; Castel et al.,
good (6.04 ± 1.26 points on the PEDro scale), and the risk of bias was 2013; Clarke-Jenssen et al., 2014; Giannotti et al., 2014; Larsson et al.,
medium. One study (1.4%) presented excellent methodological 2015; Latorre Román et al., 2015; Sañudo et al., 2015; Ericsson et al.,
quality (Arroyo-Fernández et al., 2022), 47 studies (69.1%) 2016; Espí-López et al., 2016; Ekici et al., 2017; Assumpção et al.,
presented good quality (Gowans et al., 2001; King et al., 2002; 2018; Kashikar-Zuck et al., 2018; Tomas-Carus et al., 2018; Wong
Schachter et al., 2003; Redondo et al., 2004; Da Costa et al., 2005; et al., 2018; Andrade et al., 2019; Atan and Karavelioğlu, 2020;
Kingsley et al., 2005; Hammond and Freeman, 2006; Munguía- Izquierdo-Alventosa et al., 2020; Izquierdo-Alventosa et al., 2021;
Izquierdo and Legaz-Arrese, 2007; Rooks, 2007; Günendi et al., Sauch Valmaña et al., 2020; Serrat et al., 2021b; Serrat et al., 2022;
2008; Mannerkorpi et al., 2009; Tomas-Carus et al., 2009; Tomas- Fonseca et al., 2021; Haugmark et al., 2021; Hernando-Garijo et al.,
Carus et al., 2018; Tomas-Carus et al., 2021; Carson et al., 2010; 2021; Arroyo-Fernández et al., 2022; de Lorena et al., 2022) provided
Sañudo Corrales et al., 2010; Núñez et al., 2011; Sañudo et al., 2011; data regarding the effect of PEBT on reducing pain in comparison to
Sañudo et al., 2015; Baptista et al., 2012; Jones et al., 2012; Kayo et al., other interventions. The majority of these studies (n = 43, with
2012; Castel et al., 2013; Chan et al., 2014; 2017; Clarke-Jenssen et al., 53 independent comparisons) assessed the immediate effect of PEBT
2014; Larsson et al., 2015; Ericsson et al., 2016; Espí-López et al., on pain, with a moderate quality of evidence. There was medium-
2016; Kurt, 2016; Kashikar-Zuck et al., 2018; Wong et al., 2018; sized effect indicating the superiority of PEBT for reducing pain
Andrade et al., 2019; Silva et al., 2019; Atan and Karavelioğlu, 2020; (SMD = −0.62; 95% CI −0.78 to −0.46; p < 0.001) (Table 2; Figure 2).

TABLE 1 PEDro scores for methodological quality and risk of bias assessment in the studies included in the systematic review and meta-analysis.
Study i1 i2 i3 i4 i5 i6 i7 i8 i9 i10 i11 Total Quality

Andrade, CP et al., 2019 Y Y Y Y N N Y Y Y Y Y 8 Good
Arcos Carmona, IM et al., 2011 Y Y N Y N N N Y N Y Y 5 Fair
Arroyo-Fernandez, R et al., 2022 Y Y Y Y Y Y Y N Y Y Y 9 Excellent
Assumpcao, A et al., 2018 Y Y N Y N N N N N Y Y 4 Fair
Astin, JA et al., 2003 Y Y N Y N N Y N N N Y 4 Fair
Atan and karavelioglu 2020 Y Y Y Y N N Y Y N Y Y 7 Good
Baptista, AS et al., 2012 Y Y Y Y N N Y Y Y Y Y 8 Good
Carson, JW et al., 2010 Y Y Y Y N N N Y Y N N 7 Good
Castel, A et al., 2013 Y Y N Y N N Y Y Y Y Y 7 Good
Cedraschi 2004 Y Y Y Y N N N N N Y Y 5 Fair
Chan, JSM et al., 2014 Y Y N Y N N N Y Y Y Y 6 Good
Chan, JSM et al., 2017 Y Y N Y N N N Y Y Y Y 6 Good
Clarke-Jenssen, A et al., 2014 Y Y N Y N N N Y Y Y Y 6 Good
Da Costa, D et al., 2005 Y Y Y Y N N Y Y Y Y Y 8 Good
Ekici, G et al., 2017 Y Y N Y N N Y N N Y Y 5 Fair
Ericsson, A et al., 2016 Y Y N Y N N Y N Y Y Y 6 Good
Espí-López, G et al., 2016 N Y Y Y N N Y N Y Y Y 6 Good
Fonseca et al., 2021 Y Y Y Y N N Y Y Y Y Y 8 Good
Fontaine and Haaz 2007 Y Y N Y N N N N N Y Y 4 Fair
Fontaine, KR et al., 2010 Y Y N Y N N N Y N Y Y 5 Fair
García-Martínez, AM et al., 2012 Y Y N Y N N N N N Y Y 4 Fair
Garrido-Ardila, EM et al., 2020 Y Y Y Y N N Y N N Y Y 6 Good
Giannotti, E et al., 2014 Y Y N Y N N N Y N Y Y 5 Fair
Gowans, SE et al., 2001 Y Y N Y N N Y Y Y Y Y 7 Good
Gunendi, Z et al., 2008 Y Y Y Y N N N N N Y Y 5 Good
Gusi, N et al., 2006 Y Y N Y N N N Y N Y Y 5 Fair
Hammond and Freeman 2006 Y Y Y Y N N N N Y Y Y 6 Good
Haugmark, T et al., 2021 Y Y Y Y N N Y Y Y Y Y 8 Good
Hernando-Garijo, I et al., 2021 Y Y N Y N N Y Y Y Y Y 7 Good
Izquierdo-Alventosa, R et al., 2020 Y Y Y Y N N Y Y Y Y Y 8 Good
Izquierdo-Alventosa, R et al., 2021 Y Y Y Y N N Y Y N Y Y 7 Good
Jones, KD et al., 2012 Y Y N Y N N N Y Y Y Y 6 Good
Kashikar-Zuck, S et al., 2018 Y Y Y Y N N N Y Y Y Y 7 Good
Kayo, AH et al., 2012 Y Y Y Y N N N N Y Y Y 6 Good
King, SJ et al., 2002 Y Y N Y N N Y N Y Y Y 6 Good
Kingsley, JD et al., 2005 Y Y N Y N N Y N Y Y Y 6 Good
Kurt 2016 Y Y N Y N N Y Y N Y Y 6 Good
Larsson, A et al., 2015 Y Y Y Y N N Y N Y Y Y 8 Good
(Continued on following page)

TABLE 1 (Continued) PEDro scores for methodological quality and risk of bias assessment in the studies included in the systematic review and meta-analysis.
Study i1 i2 i3 i4 i5 i6 i7 i8 i9 i10 i11 Total Quality

Latorre-Román, PA et al., 2015 Y Y N Y N N N Y N Y Y 5 Fair
Lorena, SB et al., 2022 Y Y Y Y N N Y N N Y Y 6 Good
Maddali-Bongi, S et al., 2016 N Y N Y N N N N N Y Y 4 Fair
Mannerkorpi, K et al., 2000 Y Y N Y N N Y N N Y Y 5 Fair
Mannerkorpi, K et al., 2009 Y Y Y Y N N Y N Y Y Y 7 Good
Martín, J et al., 2014 Y Y N Y N N N N N Y Y 4 Fair
Munguía-Izquierdo and Legaz 2007 Y Y N Y N N N Y Y Y Y 6 Good
Núñez, M et al., 2011 Y Y Y Y N N N Y Y Y Y 7 Good
Redondo, JR et al., 2004 Y Y N Y N N Y N Y Y Y 6 Good
Richards 2002 Y Y N N N N Y N Y Y Y 5 Fair
Rooks 2007 Y Y Y Y N N Y N Y Y Y 7 Good
Sañudo-Corrales, B et al., 2010 Y Y N Y N N N Y Y Y Y 6 Good
Sañudo-Corrales et al., 2011 Y Y Y Y N N Y Y Y Y Y 8 Good
Sañudo-Corrales, B et al., 2015 Y Y Y Y N N N Y Y Y Y 7 Good
Sauch-Valmaña, G et al., 2020 N Y N Y N N Y Y N Y Y 5 Fair
Schachter, CL et al., 2003 Y Y Y N N N N Y Y Y Y 6 Good
Sencan, S et al., 2004 N Y N Y N N N Y N Y N 3 Poor
Serrat, M et al., 2020 Y Y N Y N N N Y Y Y Y 6 Good
Serrat, M et al., 2021a Y Y N Y N N N Y Y Y Y 6 Good
Serrat, M et al., 2021b Y Y Y Y N N Y N Y Y Y 7 Good
Serrat, M et al., 2022 Y Y N Y N N Y N Y Y Y 6 Good
Silva et al., 2019 Y Y Y Y N N Y Y Y Y Y 8 Good
Tomas-Carus, P et al., 2007 Y Y N Y N N N Y N Y Y 5 Fair
Tomas-Carus, P et al., 2009 Y Y N Y N N Y Y N Y Y 6 Good
Tomas-Carus, P et al., 2018 Y Y Y Y N N Y Y N Y Y 7 Good
Tomas-Carus, P et al., 2021 Y Y Y Y N N Y N N Y Y 6 Good
Wigers, SH et al., 1996 Y Y N Y N N Y N Y Y Y 6 Good
Windthorst, P et al., 2017 Y Y N Y N N N N N Y Y 4 Fair
Wong, A et al., 2018 Y Y Y Y N N N N N Y Y 5 Good
Zijlstra 2005 Y Y Y Y N N N N N Y Y 5 Fair
Abbreviations: i1, Eligibility criteria; i2, Random allocation; i3, Concealed allocation; i4, Baseline comparability; i5, Blind subjects; i6, Blind therapists; i7, Blind assessors; i8, Adequate follow-up;
i9, Intention-to-treat analysis; i10, Between-group comparisons; i11, Point estimates and variability; Y, yes; N, No. Note: Eligibility criteria item does not contribute to total score.
In addition, PEBT led to a 1.4-point reduction in the VAS for pain To examine the effects of specific modes of PEBT on pain
(95% CI −1.5–−1.27; p < 0.001). Visual analysis of the forest plot reduction, we performed subgroup analysis. Circuit-based
revealed asymmetry, thus indicating a high risk of publication bias exercises had a medium-sized effect on pain reduction
(Egger p = .16). The trim-and-fill estimation method revealed 32% (SMD = −0.54; 95% CI −0.72 to −0.38; p < 0.001), and exercise-
variation from the original effect (SMD = −0.8) ((Supplementary movement technique had a large-sized effect on pain reduction
Figure S1). This indicates that the original pooled effect is (SMD = −1.1; 95% CI −1.48–−0.63; p < 0.001); the quality of
underestimated due to the risk of publication bias. The level of evidence was high ((Supplementary Table S2).
heterogeneity was low-to-moderate (I2 = 34.1%; Q = 78.9 (df = 52); Additional subgroup analyses were performed to assess the
p = 0.01). Sensitivity analysis showed a maximum variation of 2.1% effect of PEBT on pain over time. Our results showed that PEBT
from the original pooled effect. had a medium-to large-sized effect on pain at the 12-week follow-up

(SMD = −0.74; 95% CI −1.03–−0.45; p < 0.001) and a small-sized
Quality
Moderate
Moderate
Abbreviations: K, number of comparisons; SMD, standardized mean difference; 95% CI, 95% Confidence interval; p, p-value; Q, Q-test; df, degree of freedom; I2, degree of inconsistency; Adj, Adjusted; % var, Percentage of variation; Incons, Inconsistency; Indir,
effect at the 24-week follow-up (SMD = −0.19; 95% CI −0.32–−0.06;
High
High
High
p = 0.04). No effect was found at 48 weeks (SMD = −0.04; 95%
CI −0.32–0.24; p = 0.78) (Supplementary Table S2).
Our findings revealed that the most effective dose of PEBT for
Pub bias
Yes
Yes
No
No
No
reducing pain in patients with FMS was 21–40 sessions
(SMD = −0.83; 95% CI −1.1 to −0.56; p < 0.001), 3 sessions per
week (SMD = −0.82; 95% CI −1.2–−0.48; p < 0.001), and 61–90 min
GRADE framework
Imprec
per session (SMD −1.08; 95% CI −1.55–−0.62; p < 0.001)

No
No
No
No
No
(Supplementary Table S3).
Indir
No
No
No
No
No 3.6 Effects of PEBT on the impact of FMS

Incons
Forty-nine studies (Mannerkorpi et al., 2000; Mannerkorpi et al.,

Yes
Yes
No
No
No
2009; Gowans et al., 2001; King et al., 2002; Richards, 2002; Astin et al.,
2003; Schachter et al., 2003; Cedraschi, 2004; Redondo et al., 2004; Da
Risk of bias
Costa et al., 2005; Kingsley et al., 2005; Zijlstra, 2005; Hammond and
Freeman, 2006; Fontaine and Haaz, 2007; Munguía-Izquierdo and
Med
Med
Med
Med
Med
Legaz-Arrese, 2007; Rooks, 2007; Tomas-Carus et al., 2007; 2018;

Carson et al., 2010; Fontaine et al., 2010; Sañudo et al., 2011; Baptista
et al., 2012; García-Martínez et al., 2012; Jones et al., 2012; Kayo et al.,
% Var
2012; Castel et al., 2013; Giannotti et al., 2014; Martín et al., 2014; Larsson
32
29
0
Trim-and-fill
et al., 2015; Latorre Román et al., 2015; Espí-López et al., 2016; Kurt,
2016; Maddali Bongi et al., 2016; Ekici et al., 2017; Assumpção et al.,
Adj SMD
Publication bias
2018; Andrade et al., 2019; Atan and Karavelioğlu, 2020; Garrido-Ardila

−0.80
−0.71
−0.36
0.56
0.48
et al., 2020; Izquierdo-Alventosa et al., 2020; Izquierdo-Alventosa et al.,

Indirect evidence; Imprec, Imprecision; Pub bias; Publication bias; Asym, Asymmetric; Sym, Symmetric; Med, Medium; QoL, quality of life.
2021; Sauch Valmaña et al., 2020; Serrat et al., 2020; Serrat et al., 2021b;
Serrat et al., 2021a; Serrat et al., 2022; Fonseca et al., 2021; Hernando-
Funnel plot P)
Garijo et al., 2021; Arroyo-Fernández et al., 2022; de Lorena et al., 2022)

Asym. (0.16)
Asym. (0.52)
Asym. (0.01)
Sym. (0.48)
Sym. (0.66)
assessed the effect of PEBT on the impact of FMS. Data from 45 studies
(with 55 independent comparisons) with a moderate quality of evidence
were analyzed, and there was a medium-sized effect indicating the
superiority of PEBT compared to other interventions in the immediate
term (SMD = −0.52; 95% CI −0.67 to −0.36; p < 0.001) (Table 2;
0.01
0.01
0.66
0.27
0.37
P
Figure 3). In addition, PEBT led to a 7.5-point reduction in scores on the

TABLE 2 Main findings of the meta-analysis to assess the immediate effect of PEBT.
Heterogeneity
FIQ questionnaire (95% CI −8.14 to −5.1; p < 0.001). Trim-and-fill

I2 (%)
34.1
40.3
14.1
7.68
8.7
estimation revealed a variation of 29% from the original pooled effect

(SMD adjusted = −0.71), thus indicating potential publication bias.
Similar to the findings for pain reduction, the publication bias observed
31.14 (29)
78.9 (52)
90.4 (54)
22.4 (26)
25.6 (22)
Q (df)
for this outcome indicates that the true effect of PEBT on FIQ was
underestimated (Supplementary Figure S2). The level of heterogeneity
was moderate (I2 = 40.3%; Q = 90.4 (df = 54); p = .01), and sensitivity
<0.001
<0.001
<0.001
<0.001
<0.001
analysis did not reveal substantial variations (5.2%) from the original
P
effect size.
Subgroup analysis based on the specific mode of PEBT used
−0.51 to −0.46
−0.67 to −0.36
−0.49 to −0.25
0.33 to 0.69
0.29 to 0.67
95% CI
showed a medium-sized effect of circuit-based exercises

Effect size
(SMD = −0.54; 95% CI −0.71 to −0.38; p < 0.001) and a low-to

medium-sized effect of exercise movement techniques
(SMD = −0.32; 95% CI −0.48 to −0.15; p = 0.001) on reducing
SMD
−0.62
−0.52
−0.36
0.51
0.48
the impact of FMS (Supplementary Table S2).

The effect of PEBT on the impact of FMS was maintained over
time and showed a medium-sized effect at 12 weeks (SMD = −0.51;
53
55
27
23
30
K
95% CI −0.84–−0.18; p = 0.003), 24 weeks (SMD = −0.27; 95%

CI −0.41–−0.15; p < 0.001) and 48 weeks (SMD = −0.3; 95%
QoL-Physical
FMS Impact
QoL-Mental
Variables
Anxiety
CI −0.45–−0.15; p < 0.001) (Supplementary Table S2).

Pain
Finally, our findings reported that the most effective dose of

PEBT for reducing in the impact of FMS is 21–40 sessions

FIGURE 2
Forest Plot of the immediate effect of PEBT on pain.
(SMD = −0.63; 95% CI -0.87 to −0.35; p < 0.001), 3 sessions per week a medium-sized effect indicating the superiority of PEBT for
(SMD = −0.57, 95% CI -1.03 to −0.12, p = 0.013), and 31–60 min per improving the physical dimension of QoL compared to other
session (SMD = −0.5, 95% CI −0.7–−0.3; p < 0.001) (Supplementary interventions (SMD = 0.51; 95% CI 0.33–0.69; p < 0.001)
Table S3). (Table 2; Figure 4A). Specifically, data from 23 studies with
27 independent comparisons indicated that PEBT led to a 9.7-
point increase in scores on the physical component of the SF-36
3.7 Effects of PEBT on the QoL-physical when assessed immediately after therapy (95% CI 6.44–13.52; p <
dimension 0.001). No risk of publication bias (Egger p = 0.48) was found
(Supplementary Figure S3), and the level of heterogeneity was very
Twenty-four studies (Mannerkorpi et al., 2000; Mannerkorpi low (I2 = 8.7%; Q = 22.4 (df = 26); p = 0.66). Sensitivity analysis
et al., 2009; Cedraschi, 2004; Redondo et al., 2004; Rooks, 2007; only showed 10.7% of variation from the original pooled effect.
Tomas-Carus et al., 2007; Tomas-Carus et al., 2009; Tomas-Carus Subgroup analysis based on the specific mode of PEBT used
et al., 2021; Sañudo Corrales et al., 2010; Arcos-Carmona et al., revealed a medium-sized effect of circuit-based exercises (SMD =
2011; Núñez et al., 2011; Sañudo et al., 2011; Baptista et al., 2012; 0.5; 95% CI 0.32–0.69; p < 0.001) but no effect of exercise movement
García-Martínez et al., 2012; Maddali Bongi et al., 2016; techniques (SMD = 0.59; 95% CI −0.11–1.28; p = 0.096)
Windthorst et al., 2017; Assumpção et al., 2018; Andrade et al., (Supplementary Table S2).
2019; Silva et al., 2019; Atan and Karavelioğlu, 2020; Sauch Subgroup analysis based on follow-up time revealed that PEBT
Valmaña et al., 2020; Serrat et al., 2021b; Serrat et al., 2021a; did not have a significant effect on physical QoL at 24 weeks (SMD =
Serrat et al., 2022) assessed the effect of PEBT on the physical 0.21; 95% CI −0.16–0.58; p = .26) or 48 weeks (SMD 0.07; 95%
dimension of QoL. The quality of evidence was high, and there was CI −0.25–0.39; p = .67) (Supplementary Table S2).

FIGURE 3
Forest Plot of the immediate effect of PEBT on FMS impact.
The most effective dose of PEBT for increasing physical QoL is medium-sized effect indicating the superiority of PEBT for improving
21–40 sessions (SMD = 0.57; 95% CI 0.32–0.79; p < 0.001), 3 sessions mental QoL compared to the other interventions when assessed
per week (SMD = 0.75; 95% CI 0.24–1.24; p = 0.004), and 31–60 min immediately after therapy (SMD = 0.48; 95% CI 0.29–0.67; p <
per session (SMD 0.55; 95% CI 0.37–0.74; p < 0.001) .001) (Table 2; Figure 4B). Across 19 studies with 23 independent
(Supplementary Table S3). comparisons, PEBT led to a 10.43-point increase in scores on the
mental component of the SF-36 at immediate assessment (95% CI
6.26–14.6; p < 0.001). No risk of publication bias was found
3.8 Effects of PEBT on the QoL-mental (Supplementary Figure S4), and the level of heterogeneity was low
dimension (I2 = 14.1%; Q = 20.97 (df = 22); p = 0.37). Sensitivity analysis showed a
6.7% variation from the original pooled effect.
The effect of PEBT on the mental dimension of QoL was assessed Regarding the specific mode of PEBT used, there was a medium-
in 20 studies (Mannerkorpi et al., 2000; Mannerkorpi et al., 2009; sized effect indicating the superiority of circuit-based exercises for
Redondo et al., 2004; Rooks, 2007; Tomas-Carus et al., 2007; Tomas- increasing the mental dimension of QoL (SMD = 0.54; 95% CI
Carus et al., 2009; Tomas-Carus et al., 2021; Sañudo Corrales et al., 0.36–0.72; p < 0.001) (Supplementary Table S2).
2010; Arcos-Carmona et al., 2011; Núñez et al., 2011; Sañudo et al., No statistically significant differences were found at 24 weeks
2011; Baptista et al., 2012; García-Martínez et al., 2012; Maddali Bongi (SMD = 0.23; 95% CI -0.13 to 0.6; p = 0.21) or 48 weeks
et al., 2016; Windthorst et al., 2017; Assumpção et al., 2018; Andrade (SMD = −0.07; 95% CI −0.32–0.3; p = 0.96) (Supplementary Table S2).
et al., 2019; Silva et al., 2019; Atan and Karavelioğlu, 2020; Sauch PEBT was found to be most effective at increasing scores on the
Valmaña et al., 2020). The quality of evidence was high, and there was a mental dimension of the SF-36 when it is applied for 21–40 sessions

FIGURE 4
Forest Plot of the immediate effect of PEBT on QoL-physical (A) and mental dimension (B).
(SMD = 0.51; 95% CI 0.28–0.73; p < 0.001), 5 sessions per week Redondo et al., 2004; Zijlstra, 2005; Hammond and Freeman, 2006;
(SMD = 1.1; 95% CI 0.55–1.63; p < 0.001) and 31–60 min per session Rooks, 2007; Günendi et al., 2008; Carson et al., 2010;
(SMD = 0.51; 95% CI 0.31– 0.71; p < 0.001) (Supplementary Arcos-Carmona et al., 2011; Baptista et al., 2012; Chan et al.,
Table S3). 2014; Chan et al., 2017; Martín et al., 2014; Sañudo et al., 2015;
Ericsson et al., 2016; Maddali Bongi et al., 2016; Ekici et al., 2017;
Assumpção et al., 2018; Tomas-Carus et al., 2018; Andrade et al.,
3.9 Effects of PEBT on anxiety 2019; Izquierdo-Alventosa et al., 2020; Serrat et al., 2020; Serrat et al.,
2021b; Serrat et al., 2021a; Serrat et al., 2022; Fonseca et al., 2021;
Thirty studies (Mannerkorpi et al., 2000; Mannerkorpi et al., Hernando-Garijo et al., 2021; Arroyo-Fernández et al., 2022)
2009; Gowans et al., 2001; Schachter et al., 2003; Cedraschi, 2004; examined the effect of PEBT on anxiety. Of these, 27 studies

FIGURE 5
Forest Plot of the immediate effect of PEBT on anxiety.
with 30 independent comparisons assessed the immediate effect of circuit-based exercises and movement exercise techniques. In our
PEBT on anxiety. The quality of evidence was high, and PEBT had a study, subgroup analysis was performed to determine the optimal
medium-sized effect on reducing anxiety compared to other total number of sessions, sessions per week and duration of each
interventions (SMD = −0.36; 95% CI −0.49–−0.25; p < 0.001) session to obtain optimal improvement for each assessed
(Table 2; Figure 5). No risk of publication bias was found outcome. For all outcomes, the most effective dose of PEBT
(Supplementary Figure S5), and the level of heterogeneity was was a total of 21–40 sessions (except for anxiety, which
very low (I2 = 7.68%; Q = 31.14 (df = 29); p = 0.37). Sensitivity required fewer sessions), 3 sessions per week (except for
analysis only showed a maximum variation of 9% from the original mental QoL, for which 5 sessions was optimal, even though
pooled effect. the SMD of 3 sessions presented a higher quality of evidence
Regarding the specific modes of PEBT, circuit-based exercises due to a higher number of included studies) and between
(SMD = −0.37; 95% CI −0.5–−0.24; p < 0.001) and exercise 31–60 min per session (except in pain, for which the most
movement techniques (SMD = −0.37; 95% CI −0.66–−0.08; p = effective duration was 61–90 min).
.013) both led to reduced levels of anxiety. Finally, PEBT showed an To date, some reviews have assessed the effect of PEBT on
effect at the 12-week follow-up (SMD = −0.24; 95% CI −0.41–−0.07; different FMS symptoms. Our review differs from previous
p = 0.007) (Supplementary Table S2). published works in the following ways: 1) it included a large
The most effective dose of PEBT for reducing anxiety in FMS number of studies; 2) it analyzed whether findings are robust by
patients was fewer than 20 sessions (SMD = −0.45; 95% performing sensitivity and subgroup analysis; 3) it included an
CI −0.62–−0.3; p < 0.001), 3 sessions per week (SMD = −0.73; assessment of the quality of the studies included for
95% CI −1.16–−0.3; p < 0.001) and 31–60 min per session each outcome and the quality of evidence for each outcome;
(SMD = −0.4; 95% CI −0.51–−0.3; p < .001) (Supplementary and 4) it examined the most effective dose of PEBT for each
Table S3). outcome.
Additionally, our results showed that PEBT–especially
circuit-based exercise (e.g., aerobic, resistance or strength
4 Discussion exercises)—is effective at reducing pain. These findings are
consistent with previous reviews, although the level of
The present systematic review with meta-analysis included confidence in our results may be higher due to the higher level
68 RCTs that examined different modalities of PEBT, such as of precision in our study (Sosa-Reina et al., 2017). Furthermore,

the positive effect of PEBT on pain reduction may be observed in number of studies that reported data from circuit-based exercise
the use of exergames (Cortés-Pérez et al., 2021) or pain was notably large.
neuroeducation programs (Saracoglu et al., 2022) to obtain Our findings suggest that the most effective dose of PEBT for
more improvements. However, our findings did not show pain management is three sessions per week for 2–4 months
statistically significant differences between exercises (such as (21–40 sessions) with each session lasting 60–90 min. Sessions
yoga or tai chi) and other therapies, in contrast to previous lasting 30–60 min are recommended for managing the impact of
reviews (Cheng et al., 2019). PEBT was shown to lead to a 1.4- the disease. In contrast, Sosa-Reina proposed a shorter duration of
point reduction in scores on the pain rating scale; while this sessions (30–60 min), a longer total period of therapy (4–6 months)
reduction does not exceed the MCID for this outcome and the same weekly frequency to observe the strongest effects on
[i.e., 2 points (Mease et al., 2011)], PEBT reduces this FMS management (Sosa-Reina et al., 2017). In addition, the results
disabling symptom by more than 10%. Muscle gain reduces obtained in this review showed that a duration of 3–6 months is
pain and is one of the most effective and fastest methods of necessary to observe improvements in depressive symptoms (Sosa-
pain control in patients with FMS (Gavi et al., 2014). Therefore, Reina et al., 2017). However, according to our results, a reduction in
PEBT-induced improvements in muscle strength and reductions anxiety levels could be observed between 1 week and 2 months if the
in muscle fatigue (Estévez-López et al., 2021) could explain the exercise is performed at least 3 days per week with a duration of
results obtained, i.e., the association between circuit-based 30–60 min.
exercises and pain reduction. In addition, PEBT could favor Although our findings have several clinical implications, some
the production of endogenous opioids and beta-endorphins, limitations must be considered. First, one of the challenges in
causing hypoalgesia due to activation in descending achieving the objectives of this study was the considerable
nociceptive inhibitory mechanisms that decrease pain diversity and variability of PEBT modes examined across studies;
sensitivity (Tan et al., 2022). even though we categorized these therapies into two groups, there
One of the most important limitations experienced by patients was still heterogeneity within each group. The risk of publication
with FMS occurs as a consequence of the enormous impact on all bias for some outcomes indicates that the original pooled effect of
areas of their lives, including physical, psychological and work PEBT on pain and the impact of FMS was underestimated. For these
factors, as assessed by the FIQ (Bennett et al., 2007). Our outcomes, the quality of evidence was downgraded due to the trim
findings suggest, with high-quality evidence, that PEBT is and fill estimation method yielding variations of greater than 10%.
effective in reducing the impact of FMS; PEBT led to a 7.5-point In addition, it is important to take into account the possible risk of
reduction in the FIQ total score, which is less than the MCID [14% selection, detection and performance biases, which could decrease
(BENNETT et al., 2009)]. Consistent with previous reviews (Kim the quality of evidence of our findings. Another limitation is the
et al., 2019; Galvão-Moreira et al., 2021), our findings showed that large variability in the control groups, as there was a small number of
circuit-based exercise (including in water-based exercises) and studies for each type of control therapy. Finally, the number of
movement-exercise techniques are effective in reducing the studies that reported data on circuit-based exercise was greater than
impact of FMS, with circuit-based exercises being the most the number of studies that reported data on exercise-movement
effective mode of PEBT. This effect may be related to the fact technique; thus, findings regarding the latter modality must be
that circuit-based exercises are the best option for reducing FMS- interpreted with caution.
related pain. The reduction in pain reduces kinesiophobia and
increases the level of activity of these patients (Martinez-
Calderon et al., 2021), thereby limiting the negative impact of 5 Conclusion
FMS symptoms.
Regarding psychological dimensions, PEBT leads to a PEBT is effective in reducing pain, the impact of FMS and
reduction in anxiety; however, in contrast to other outcomes, anxiety and increasing physical and mental QoL in patients with
exercise-movement technique is the most effective mode of PEBT FMS in comparison to other classical therapeutic options, such as
for this outcome. Tai Chi, yoga and meditation exercises as electrotherapy, balneotherapy, drugs, relaxation or usual care.
monotherapy or adjunctive therapy have been shown to reduce Circuit-based exercises (e.g., aerobic, strength, flexibility,
anxiety, depression or sleep disorders (Saeed et al., 2019). For resistance exercises) are effective for all these outcomes, especially
example, yoga has shown interesting results in reducing pain, for reducing FMS impact and increasing physical and mental QoL,
anxiety and catastrophizing among individuals with FMS, while exercise-movement techniques (e.g., Tai Chi, yoga, Pilates) are
thereby increasing their functional capacity and QoL especially effective for reducing pain and anxiety. It is possible that
(Lazaridou et al., 2019). PEBT led to a 9-7-point increase and exercise movement techniques may be effective for increasing QoL,
a 10.43-point increase in physical and mental SF-36 scores, but more studies are needed to confirm this effect. In general, the
respectively. Thus, PEBT is considered an excellent therapy for most appropriate dose of PEBT is 21–40 sessions, 3 times per week,
improving QoL because these values are important clinical with a duration of 31–60 min; however, there are exceptions for
differences between pre- and posttreatment. Circuit-based some outcomes, such as pain and mental QoL. Finally, the effect of
exercises are the most effective mode of PEBT for improving PEBT is not maintained over time; it weakens or disappears at
QoL. However, the very low number of studies examining the 24 and 48 weeks after the end of the treatment. Our findings
effects of exercise-movement techniques may mask any potential confirmed that PEBT is an excellent therapy used by clinicians to
effect. Finally, although exercise is effective at reducing anxiety, manage the disabling symptoms of FMS, although more research is
the effect of both exercise modalities was similar. However, the necessary to obtain more robust findings.

Data availability statement the manuscript. All authors read and approved the final
manuscript.
The datasets presented in this article are not readily available
because Data are available requesting to the corresponding author.
Requests to access the datasets should be directed to [email protected]. Conflict of interest
The authors declare that the research was conducted in the
Author contributions absence of any commercial or financial relationships that could be
construed as a potential conflict of interest.
DR-A, EO-G and RL-V conceptualized the study. DR-A,
MM-G, EO-G and RL-V contributed to literature search,
screening, and data extraction. MCL-R and IC-P contributed Supplementary material
in the assessment of risk of bias and data validation. EO-G, IC-P
and RL-V contributed to statistical analysis. DR-A, EO-G and The Supplementary Material for this article can be found online
RL-V were major contributors in writing the Manuscript. EO-G at: https://www.frontiersin.org/articles/10.3389/fphys.2023.1170621/
and RL-V are responsible for review and modification of full#supplementary-material
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TYPE Systematic Review

PUBLISHED 12 April 2023

Optimal dose and type of exercise

RECEIVED 22 February 2023

ﬁbromyalgia, exercise therapy, pain, quality of life, anxiety, women, disability,

Frontiers in Physiology 01 frontiersin.org

1 Introduction large variety of aerobic, resistance, strength, balance, and

Frontiers in Physiology 02 frontiersin.org

Frontiers in Physiology 03 frontiersin.org

groups was calculated to compare our results with the minimum

Frontiers in Physiology 04 frontiersin.org

Frontiers in Physiology 05 frontiersin.org

Study i1 i2 i3 i4 i5 i6 i7 i8 i9 i10 i11 Total Quality

Arcos Carmona, IM et al., 2011 Y Y N Y N N N Y N Y Y 5 Fair

Arroyo-Fernandez, R et al., 2022 Y Y Y Y Y Y Y N Y Y Y 9 Excellent

Assumpcao, A et al., 2018 Y Y N Y N N N N N Y Y 4 Fair

Astin, JA et al., 2003 Y Y N Y N N Y N N N Y 4 Fair

Atan and karavelioglu 2020 Y Y Y Y N N Y Y N Y Y 7 Good

Baptista, AS et al., 2012 Y Y Y Y N N Y Y Y Y Y 8 Good

Carson, JW et al., 2010 Y Y Y Y N N N Y Y N N 7 Good

Castel, A et al., 2013 Y Y N Y N N Y Y Y Y Y 7 Good

Cedraschi 2004 Y Y Y Y N N N N N Y Y 5 Fair

Chan, JSM et al., 2014 Y Y N Y N N N Y Y Y Y 6 Good

Chan, JSM et al., 2017 Y Y N Y N N N Y Y Y Y 6 Good

Clarke-Jenssen, A et al., 2014 Y Y N Y N N N Y Y Y Y 6 Good

Da Costa, D et al., 2005 Y Y Y Y N N Y Y Y Y Y 8 Good

Ekici, G et al., 2017 Y Y N Y N N Y N N Y Y 5 Fair

Ericsson, A et al., 2016 Y Y N Y N N Y N Y Y Y 6 Good

Espí-López, G et al., 2016 N Y Y Y N N Y N Y Y Y 6 Good

Fonseca et al., 2021 Y Y Y Y N N Y Y Y Y Y 8 Good

Fontaine and Haaz 2007 Y Y N Y N N N N N Y Y 4 Fair

Fontaine, KR et al., 2010 Y Y N Y N N N Y N Y Y 5 Fair

García-Martínez, AM et al., 2012 Y Y N Y N N N N N Y Y 4 Fair

Garrido-Ardila, EM et al., 2020 Y Y Y Y N N Y N N Y Y 6 Good

Giannotti, E et al., 2014 Y Y N Y N N N Y N Y Y 5 Fair

Gowans, SE et al., 2001 Y Y N Y N N Y Y Y Y Y 7 Good

Gunendi, Z et al., 2008 Y Y Y Y N N N N N Y Y 5 Good

Gusi, N et al., 2006 Y Y N Y N N N Y N Y Y 5 Fair

Hammond and Freeman 2006 Y Y Y Y N N N N Y Y Y 6 Good

Haugmark, T et al., 2021 Y Y Y Y N N Y Y Y Y Y 8 Good

Hernando-Garijo, I et al., 2021 Y Y N Y N N Y Y Y Y Y 7 Good

Izquierdo-Alventosa, R et al., 2020 Y Y Y Y N N Y Y Y Y Y 8 Good

Izquierdo-Alventosa, R et al., 2021 Y Y Y Y N N Y Y N Y Y 7 Good

Jones, KD et al., 2012 Y Y N Y N N N Y Y Y Y 6 Good

Kashikar-Zuck, S et al., 2018 Y Y Y Y N N N Y Y Y Y 7 Good

Kayo, AH et al., 2012 Y Y Y Y N N N N Y Y Y 6 Good

King, SJ et al., 2002 Y Y N Y N N Y N Y Y Y 6 Good

Kingsley, JD et al., 2005 Y Y N Y N N Y N Y Y Y 6 Good

Kurt 2016 Y Y N Y N N Y Y N Y Y 6 Good

Larsson, A et al., 2015 Y Y Y Y N N Y N Y Y Y 8 Good

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Frontiers in Physiology 06 frontiersin.org

Study i1 i2 i3 i4 i5 i6 i7 i8 i9 i10 i11 Total Quality

Lorena, SB et al., 2022 Y Y Y Y N N Y N N Y Y 6 Good

Maddali-Bongi, S et al., 2016 N Y N Y N N N N N Y Y 4 Fair

Mannerkorpi, K et al., 2000 Y Y N Y N N Y N N Y Y 5 Fair

Mannerkorpi, K et al., 2009 Y Y Y Y N N Y N Y Y Y 7 Good

Martín, J et al., 2014 Y Y N Y N N N N N Y Y 4 Fair

Munguía-Izquierdo and Legaz 2007 Y Y N Y N N N Y Y Y Y 6 Good