Behaviour Research and Therapy 158 (2022) 104188 Contents lists available at ScienceDirect Behaviour Research and Therapy journal homepage: www.elsevier.com/locate/brat Effectiveness of two video-based multicomponent treatments for fibromyalgia: The added value of cognitive restructuring and mindfulness in a three-arm randomised controlled trial Mayte Serrat a, b, Klara Albajes c, 1, Jaime Navarrete d, e, 1, Miriam Almirall a, Enrique Lluch Girbés f, Randy Neblett g, Juan V. Luciano d, e, h, 2, Jenny Moix c, 2, Albert Feliu- Soler d, e, h, *, 2 a Unitat d’Expertesa en Síndromes de Sensibilització Central, Servei de Reumatologia, Vall d’Hebron Hospital, 08035, Barcelona, Spain b Escoles Universitàries Gimbernat, Autonomous University of Barcelona, Bellaterra (Cerdanyola del Vallès), 08193, Barcelona, Spain c Department of Basics, Developmental and Educational Psychology, Faculty of Psychology, Autonomous University of Barcelona, Bellaterra (Cerdanyola del Vallès), 08193, Barcelona, Spain d Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, 08950, Barcelona, Spain e Psychological Research in Fibromyalgia and Chronic Pain (AGORA Research Group), Teaching, Research & Innovation Unit, Parc Sanitari Sant Joan de Déu, St. Boi de Llobregat, Spain f Department of Physiotherapy, Universitat de València, Valencia, Spain g PRIDE Research Foundation, Dallas, TX, USA h Department of Clinical and Health Psychology, Faculty of Psychology, Autonomous University of Barcelona, Bellaterra (Cerdanyola del Vallès), 08193, Barcelona, Spain A R T I C L E I N F O A B S T R A C T Keywords: Background/objectives: The aim of this study was to examine the effectiveness of two video-based multicompo­ Fibromyalgia nent programs (FIBROWALK) and the Multicomponent Physiotherapy Program (MPP) for patients with fibro­ Virtual multicomponent treatment myalgia (FM) compared to treatment-as-usual (TAU) only. We posit that FIBROWALK, due to inclusion of specific Pain neuroscience education psychological ingredients (cognitive restructuring and mindfulness), can produce additional clinical benefits Therapeutic exercise Cognitive behaviour therapy when compared to TAU or MPP alone. Mindfulness Methods: A total of 330 patients with FM were recruited and randomly allocated (1:1:1) to TAU only, TAU + FIBROWALK, or TAU + MPP. FIBROWALK and MPP consisted of weekly videos on pain neuroscience education, therapeutic exercise and self-management patient education, but only the FIBROWALK intervention provided cognitive restructuring and mindfulness. Both programs were structurally equivalent. Between-group differences in functional impairment, pain, kinesiophobia, anxious-depressive symptoms and physical functioning were evaluated at post-treatment following Intention-To-Treat and complete-case approaches. Results: Compared to TAU only, individuals in the FIBROWALK arm showed larger improvements in all clinical outcomes; similarly, participants in the MPP program also showed greater improvements in functional impairment, perceived pain, kinesiophobia, depressive symptoms compared to TAU only. The FIBROWALK intervention showed superior effects in improving pain, anxiety and depressive symptoms and physical functioning compared to MPP. Conclusions: This RCT supports the short-term effectiveness of the video-based multicomponent programs FIBROWALK and MPP for FM and provides evidence that cognitive-behavioural and mindfulness-based tech­ niques can be clinically useful in the context of physiotherapeutic multicomponent treatment programs. Trial registration number: NCT04571528. * Corresponding author. Department of Clinical and Health Psychology, Universitat Autònoma de Barcelona (UAB), C/ de la Fortuna s/n, 08193, Cerdanyola del Vallès, Spain. E-mail addresses: mserrat@vhebron.net, malmirall@vhebron.net (M. Serrat), k.albajes.eizaguirre@gmail.com (K. Albajes), jaime.navarrete@sjd.es (J. Navarrete), malmirall@vhebron.net (M. Almirall), enrique.lluch@uv.es (E. Lluch Girbés), RandyNeblett@pridedallas.com (R. Neblett), juanvicente.luciano@uab.cat (J.V. Luciano), jenny.moix@uab.cat (J. Moix), albert.feliu@uab.cat (A. Feliu-Soler). 1 Mayte Serrat, Klara Albajes, and Jaime Navarrete contributed equally to this article and should be considered co-first authors. 2 These authors share senior authorship. https://doi.org/10.1016/j.brat.2022.104188 Received 21 February 2022; Received in revised form 28 June 2022; Accepted 1 September 2022 Available online 8 September 2022 0005-7967/© 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). M. Serrat et al. Behaviour Research and Therapy 158 (2022) 104188 1. Introduction greatest effect sizes in this meta-analysis. A separate systematic review determined that CBT is the most common psychological intervention Fibromyalgia (FM) is a complex and highly prevalent disease (2–4% used for treating FM, both standalone and within multidisciplinary in the general population) characterized by widespread musculoskeletal programs (Albajes & Moix, 2021). The efficacy of CBT has been pain, and often accompanied by symptoms of fatigue, sleep disturbance, demonstrated in many studies, resulting in treatment improvements in cognitive problems, and psychological distress, which is usually diag­ many core FM symptoms, including pain, fatigue, depression, psycho­ nosed in women between the ages of 20 and 50 years (Häuser et al., logical well-being, and physical functioning (Albajes & Moix, 2021; 2015). People with FM typically present with comorbid psychiatric Bernardy, Klose, Welsch, & Häuser, 2018; Glombiewski et al., 2010; disorders, particularly major depressive disorder (63% of FM patients Kundakci et al., 2021; Macfarlane et al., 2017; Sosa-Reina et al., 2017). with lifetime depression) but also bipolar disorder, panic disorder, or The American Psychological Association division 12 (Society of Clinical post-traumatic stress disorder (Kleykamp et al., 2021; Lichtenstein, Psychology division of the APA) rated CBT interventions for FM as Tiosano, & Amital, 2018). These comorbidities, in turn, can aggravate having strong research support (https://div12.org/diagnosis/fibr the negative influence of pain on health-related quality of life (Gal­ omyalgia/). vez-Sánchez, Duschek, & Reyes Del Paso, 2019). In addition to CBT-based approaches, mindfulness training has been FM represents a great challenge for national health services because shown to be effective in people with FM (Haugmark, Hagen, Smedslund, of the lack of curative treatment options. The efficacy of pharmacolog­ & Zangi, 2019; Pérez-Aranda, Andrés-Rodríguez, et al., 2019). For ical approaches alone is generally limited, and more generalized clinical instance, Mindfulness-Based Stress Reduction has demonstrated treat­ effects have been found for non-pharmacological interventions (Perrot ment improvements in functional impairment, anxiety and depressive & Russell, 2014). In response to the increased evidence of efficacy of symptoms in FM subjects (Pérez-Aranda, Feliu-Soler, et al., 2019). non-pharmacological modalities, the 2016 revised European League of Mechanisms of this intervention seem to be related to a decreased pain Association of Rheumatology recommendations point to the need to catastrophizing and increased self-efficacy, pain acceptance and psy­ increase the implementation of non-pharmacological interventions chological flexibility (Pardos-Gascón, Narambuena, Leal-Costa, & gradually and sequentially in the treatment of FM (Macfarlane et al., van-der Hofstadt-Román, 2021; Pérez-Aranda, Feliu-Soler, et al., 2019; 2017; Okifuji & Hare, 2010). Turner et al., 2016). Though these treatments are traditionally provided In this regard, education is a fundamental ingredient of many face-to-face, these psychological approaches have shown positive results treatment programs for managing FM symptoms and is typically used as in online formats in individuals with FM (Bernardy, Klose, Welsch, & a first-line therapeutic option (Cunningham & Kashikar-Zuck, 2013). Häuser, 2019; Davis & Zautra, 2013). Increased knowledge about pain mechanisms and the FM diagnosis itself In light of the above, PNE, therapeutic exercises, CBT-based tech­ through education has been associated with positive effects in niques, and mindfulness training are the four non-pharmacological self-management skills and health outcomes in FM subjects (Camerini, therapy approaches that have the most published evidence for FM Camerini, & Schulz, 2013; Musekamp et al., 2019). Patients who are management (Aman, Jason Yong, Kaye, & Urman, 2018). While the first well-informed regarding their disease, prognosis and two approaches are more in the area of physiotherapy, the others tend to symptom-management strategies are better prepared to cope with the belong to the field of psychotherapy. There is burgeoning interest in the disease and thereby reduce its consequences (De Miquel et al., 2010). scientific literature in integrating these therapies and evaluating the Furthermore, when comparing different types of pain education, there specific contribution of each one within chronic pain treatment pro­ are clear differences between classical biomedical education (i.e., con­ grams (Conversano & Di Giuseppe, 2021; Merlo, 2019). In this regard, tents related to pathophysiology and biomechanics) and Pain Neuro­ an interdisciplinary treatment approach, using multicomponent empir­ science Education (PNE) (i.e., contents related to pain neurobiology and ically validated therapeutic techniques within a biopsychosocial pain processing). PNE is based on the reconceptualization of perspective, is considered the best treatment model for FM (De Miquel pain-related cognitive factors, within a biopsychosocial model, empha­ et al., 2010; Häuser, Bernardy, Arnold, Offenbächer, & Schiltenwolf, sizing that any evidence of danger or safety can increase or decrease the 2009; Macfarlane et al., 2017; Rivera et al., 2006). Multicomponent patient’s pain experience (Moseley & Butler, 2015). A recent systematic treatment approaches are recommended by most of national and inter­ review has supported the efficacy of PNE in people with chronic national FM treatment guidelines (Rivera et al., 2006; Thieme, Mathys, musculoskeletal pain in terms of improvements in pain catastrophizing, & Turk, 2017). Although there is evidence that multidisciplinary ap­ pain-related disability, inactivity, and avoidance behaviours (Louw, proaches that integrate physiotherapy and psychology components can Puentedura, Zimney, & Schmidt, 2016). Due to the mounting evidence be superior to physiotherapy alone for subjects with general chronic of the beneficial effects of PNE in people with FM, it is progressively pain conditions, this has not yet been fully evaluated in subjects with FM becoming a standard treatment modality for this population (Amer-­ (Kamper et al., 2015; Wilson & Cramp, 2018). Cuenca et al., 2020; Moseley, 2003). FIBROWALK is a multicomponent treatment program, involving 2-h It is also important to note that PNE might be more effective when weekly sessions over 12 weeks, that was specifically designed for, and combined with other techniques such as therapeutic exercise or cogni­ tested with, individuals with FM (Serrat et al., 2020a, 2021b). It involves tive behavioural therapy (CBT; Moseley et al., 2017). There is solid five components, including PNE (sessions 1–10), therapeutic exercise evidence that therapeutic exercise can result in significant improvments (sessions 2–9), self-management patient education (sessions 2–9; in core FM symptoms such as pain, depressive symptomatology, sleep, 11–12), CBT techniques (cognitive restructuring; sessions 8–9; 11–12), fatigue, global well-being, and health-related quality of life (Kundakci and mindfulness training (sessions 2–9; 11–12) in a group-based format. et al., 2021; Sosa-Reina et al., 2017). Frequently recommended exercises Traditionally, physiotherapists have been responsible for PNE, thera­ for FM include low-impact aerobic exercises, stretching, balance peutic exercise, and self-management patient education and psycholo­ training, posture correction, and gentle strengthening exercises adapted gists have been responsible for teaching CBT and mindfulness to a patient’s current physical state (e.g., Serrat, Almirall, et al., 2020). techniques. A previous randomised controlled trial (RCT) has shown Psychotherapeutic approaches have also been used for treating FM. A that the FIBROWALK program (vs. usual care) was effective (with systematic review and meta-analysis found that psychological therapies medium-to-large effect sizes) for significantly improving functional for FM were associated with improvements in depression symptoms, impairment, pain, kinesiophobia, physical function, fatigue, anxiety, catastrophizing, sleep disturbance, functional status, and short- and and depressive symptoms in a sample of patients with FM (Serrat, long-term pain reduction (Glombiewski et al., 2010). These outcomes Sanabria-Mazo, et al., 2021). were determined to be comparable to traditional FM treatment modal­ Recently, a video-based version, including all FIBROWALK compo­ ities, including pharmacological treatments. CBT demonstrated the nents, was adapted into a home-based format and tested in a pilot RCT 2 M. Serrat et al. Behaviour Research and Therapy 158 (2022) 104188 during the first Spanish COVID-19 lockdown (Serrat, Coll-Omaña, et al., Sensitivity Syndromes Specialised Unit and were assessed by a rheu­ 2021). The goal of this online version was to provide clinical support to matologist and a physical therapist to ensure they met the selection patients with FM who were unable to attend face-to-face treatment. The criteria. The inclusion criteria were as follows: (a) 18–75 years of age; online FIBROWALK program was found to be effective (with (b) fulfilment the FM classification criteria according to 2010/2011 small-to-moderate effect sizes) for improving patient-reported func­ American College of Rheumatology (Wolfe et al., 2010), i.e., widespread tional impairment and other relevant FM symptoms (Serrat, pain index (WPI) ≥7 and symptom severity (SS) scale score ≥5 or WPI Coll-Omaña, et al., 2021; Serrat, Sanabria-Mazo, et al., 2021). It is well 3–6 and SS scale score ≥9, symptoms have been present at a similar level known that efficacious online interventions have several advantages for at least 3 months, and the patient does not have a disorder that would over face-to-face interventions, including cost, convenience, and avail­ otherwise explain the pain; (c) being able to understand Spanish; and (d) ability for those patients with limited mobility and transportation op­ written informed consent. Individuals participating in concurrent or tions (Andersson, 2018; Andersson & Titov, 2014). past RCTs (during the previous year) or suffering any comorbidity such Determining the effects of specific physiotherapy and psychothera­ as severe mental disorders (i.e., psychosis) or neurodegenerative dis­ peutic modalities can provide new clues for refining and improving eases (i.e., Alzheimer) that would have limited the ability of the patient treatment efficacy. Therefore, the primary aim of this RCT was to to participate in the RCT were excluded. evaluate the effectiveness of two video-based multicomponent treat­ ment programs for FM, one that integrated physiotherapy and psycho­ 2.4. Procedure therapeutic modalities (i.e., FIBROWALK) and one that only used physiotherapy techniques (i.e., Multicomponent Physiotherapy Pro­ The study was carried out in the context of routine clinical practice at gram; MPP), and to compare them to treatment-as-usual (TAU) only. the Vall d’Hebron University Hospital - Central Sensitivity Syndromes Treatment effectiveness of the two programs was determined by im­ Specialised Unit. That is, all participants were provided by their rheu­ provements in patient-reported functional impairment (primary matologist with an overview of the study aims when they visited the outcome), pain, anxious-depressive symptoms, kinesiophobia, and hospital. COVID safety measures were followed. Participants were told physical function. Our hypotheses were as follows: It was expected that that they would receive a potentially effective treatment in addition to both FIBROWALK and MPP arms, which were equivalent in terms of the usual one that the Unit usually provides. Those interested in treatment dosage, would show greater improvements in primary and participating signed informed consent and were told that their data secondary outcomes when compared to TAU alone (hypothesis 1). would be used in this study. Participants were informed about their right Furthermore, it was expected that FIBROWALK would result in better to withdraw from the research at any time, with the assurance that they improvement in anxiety and depressive symptoms compared to MPP could continue to receive usual care. They were asked to complete an because CBT and mindfulness techniques have been shown to have online questionnaire, gathering sociodemographic and clinical infor­ significant effects on these variables (Etzelmueller et al., 2020; Spij­ mation, and all study outcome measures. The online measures were kerman, Pots, & Bohlmeijer, 2016) (hypothesis 2). In addition to completed both at pre- and at post-treatment. assessing statistical significance, the number-needed to treat (NNT) Participants who voluntarily agreed to participate in the study were index was computed to allow findings from this study to be more assigned to an alphanumeric code list and were randomised (1:1:1 ratio) meaningful to clinicians. We expected a lower NNT in both active using SPSS v25 to receive either TAU only, TAU + video-based FIBRO­ treatment arms when compared to TAU alone (hypothesis 3) as well as a WALK or TAU + video-based MPP. Numbered sealed envelopes which lower NNT for FIBROWALK when compared to MPP (hypothesis 4). As included information sheets related to participant allocation were used far as we know, this was the first study to assess the unique contribution within the randomization process. The envelopes were distributed by a of cognitive restructuring and mindfulness training in a multicomponent nurse from the Vall d’Hebron University Hospital - Central Sensitivity treatment program for the management of FM. Syndromes Specialised Unit. Neither the participants nor the therapist responsible for the treatments were blinded to the participants’ allo­ 2. Methods cated intervention. However, the nursing staff who coordinated the online assessments were blinded to the participants’ treatment 2.1. Design allocation. A three-arm randomised controlled trial (RCT) was carried out, with 2.5. Treatment interventions assessments at pre- and post-treatment. This RCT was approved by the Ethics Committee of Clinical Investigation (PR(AG)249/2020), posted Both FIBROWALK and MPP were delivered as add-ons to TAU. and registered in Clinicaltrials.gov (NCT04571528) and was conducted Subjects participated in no additional treatments during the study. TAU in accordance with the guidelines issued by the Consolidated Standards care in the Vall d’Hebron University Hospital - Central Sensitivity Syn­ of Reporting Trials (CONSORT; Moher et al., 2012). dromes Specialised Unit included: (a) prescribed medications for FM (i. e., amitriptyline, duloxetine, pregabalin and/or tramadol at low doses) 2.2. Sample size adapted to each patient’s needs and (b) written advice on PNE and aerobic exercise adapted to the physical capacities of the patients. The required sample size was estimated to be n = 51 participants per Subjects in the TAU group were offered the opportunity to participate in study arm, considering a moderate effect size (Cohen’s d = 0.50) for the the FIBROWALK program upon study completion. between-group differences at post-treatment for the primary outcome (i. The video-based FIBROWALK program consisted of weekly 60-min e., Revised Fibromyalgia Impact Questionnaire total score) with an α = videos that were presented over the course of 12 weeks. Subjects .05 and power 1-b = 0.80. Expecting an attrition of at least 20%, the participated in the virtual training from home. Each video was required sample size was nearly doubled so that small differences could comprised of different components of the program. The FIBROWALK be detected between the active treatment arms. intervention included PNE, therapeutic physical exercise, Self- management Patient Education, CBT techniques (mainly cognitive 2.3. Participants restructuring), and mindfulness training. PNE was based on the book “Explain Pain” (Moseley & Butler, 2017) and was the essential constit­ A total of 337 patients with FM participated in the study from uent that directed the approach taken by all the procedures involved in September 2020 to January 2021. All participants were consecutively FIBROWALK. Therapeutic physical exercise interventions were designed recruited from the Vall d’Hebron University Hospital - Central from the recommendations of the American College of Sports Medicine 3 M. Serrat et al. Behaviour Research and Therapy 158 (2022) 104188 and were taught from the same procedures described elsewhere (Serrat, 2.6.1. Primary outcome Sanabria-Mazo, et al., 2020). The Self-management Patient Education The Fibromyalgia Impact Questionnaire Revised (FIQR; Bennett et al., was comprised of different educational components aimed at teaching 2009) was used to assess the functional impairment experienced by patients how psychosocial stressors can impact pain perception and participants during the previous week. The FIQR includes a total of 21 ways of managing symptoms and improving health and well-being. items, scored on a 0–10 numerical scale, which are distributed into three Specifically, patients were taught strategies for increasing activity, dimensions: physical dysfunction (ranging from 0 to 30), overall impact improving sleep quality, increasing autonomy, coping better with stress (ranging from 0 to 20), and intensity of symptoms (ranging from 0 to 50) and other FM symptoms, enhancing treatment adherence, preventing with a total possible score of 100. Higher scores indicate greater func­ relapses/aggravations, and developing a greater ability to live a mean­ tional impairment. The Spanish version of the FIQR has demonstrated ingful life despite pain. CBT techniques, mainly cognitive restructuring, satisfactory internal consistency (Luciano, Aguado, Serrano-Blanco, were introduced for improving mood, reducing anxiety, enhancing Calandre, & Rodriguez-Lopez, 2013; Cronbach’s α = 0.91); in our adaptive emotional regulation responses, reducing catastrophic thinking sample, the internal consistency of the FIQR was found to be excellent about pain, and promoting positive behaviour changes towards a (α = 0.94). healthier lifestyle. Patients were taught how to identify automatic negative thoughts and to challenge them with more rational responses, 2.6.2. Secondary outcomes including recognizing and removing cognitive biases and correcting The Visual Analog Scale (VAS) for pain (i.e., intensity of perceived false beliefs and assumptions. Mindfulness training included meditation pain during last week, from 0 = “no pain”, to 10 = “unbearable pain”) practices based on Mindfulness-Based Stress Reduction (Kabat-Zinn, from the FIQR was used to assess pain intensity (Bennett et al., 2009). 2013). This training was aimed at changing the relationship with one’s The Tampa Scale for Kinesiophobia (TSK; Miller, Kori, & Todd, 1991) thoughts (to accept thoughts nonjudgmentally without trying to change was used to assess fear of movement. This scale comprises 11 items their content) in order to foster alternative and healthier ways of relating which are scored with a 4-point Likert scale (total score ranging from 11 and responding to personal life challenges, including chronic pain. For a to 44). Higher scores are indicative of greater pain and fear of move­ more detailed description of the FIBROWALK contents, see the supple­ ment. The Spanish version of the TSK has demonstrated satisfactory mentary tables (Supplementary Tables S1 and S3). internal consistency (α = 0.79; Gómez-Pérez, López-Martínez, & Participants allocated to the video-based MPP training received all Ruiz-Párraga, 2011). The α for the TSK was 0.89 in our sample. aspects of the FIBROWALK arm except for cognitive restructuring and The Hospital Anxiety and Depression Scale (HADS; Zigmond & Snaith, mindfulness training. The length of time spent on each component of the 1983). It includes two main dimensions (anxiety and depression), with 7 MPP training (including PNE, therapeutic physical exercise therapy, and items each, which are scored with a 4-point Likert scale. The scores of self-management patient education) was slightly longer compared to the HADS subscales range from 0 to 21 with higher scores reflecting those in the FIBROWALK in order to match the overall treatment doses higher symptom severity. The Spanish version of the HADS has of 1 h per week for 12 weeks between the two active arms. See Sup­ demonstrated satisfactory internal consistency for anxiety (α = 0.83) plementary Tables S2 and S3 for more details. and depression (α = 0.87) subscales (Luciano, Barrada, Aguado, Osma, To verify that participants adhered to FIBROWALK and MPP in­ & García-Campayo, 2014). In this work, the α was 0.84 and 0.86 for terventions, participants were asked to complete a brief online ques­ HADS-A and HADS-D, respectively. tionnaire (5–10 items) every week. This questionnaire asked for The Physical Function subscale from the 36-Item Short Form Survey (SF- verification of follow-through with homework exercises (e.g., meditation 36; Ware & Sherbourne, 1992) assessed perceived level of physical practices, guided relaxation exercises, therapeutic exercise recommen­ functioning. This subscale includes 10 items, each scored with a 3-point dations) and for one’s understanding of very basic concepts explained in Likert scale. Total scores are transformed to obtain scores that can range the videos (e.g., “Please, provide a short example of a catastrophic from 0 to 100, with higher scores indicate better physical functioning. thought”). These weekly questionnaires were used for the early detection The Spanish version of the physical function SF-36 subscale has shown of potential adherence issues (e.g., not watching the videos, not doing the satisfactory internal consistency (α = 0.94; Alonso, Prieto, & Antó, homework) as well as to prevent potential dropouts. The first author (MS) 1995). The α in our sample was .84. supervised all participants and provided remote guidance. She is both a physical therapist (>17 years of experience) and a health psychologist 2.7. Statistical analysis (>8 years of experience). In addition, she has also been trained in CBT and mindfulness. Every week, the therapist (MS) contacted (via SMS and/or All study outcomes were analyzed with descriptive statistics and telephone calls) those participants who did not answer the questionnaire expressed as means and standard deviations (SD) for quantitative vari­ or reported issues with participation (e.g., not being able to do the ables, and percentages (%) and frequencies (f) for categorical variables. homework, watch the videos, answer the questionnaire, etc.) and helped The Levene test was used to evaluate the equality of variances of them develop solutions for enhancing adherence. If necessary, individuals continuous variables, and Kolmogorov-Smirnov was used to verify who were unable to view or answer the questionnaire in a specific week sample normality and distribution. could request an extension of the date. There was no therapeutic inter­ Baseline between-group differences were calculated for both action with the participants, but participants were invited to contact the continuous and categorical variables. MANOVA was used to assess therapist by email if they experienced any problems. Approximately 24 h baseline differences in continuous variables, whereas the χ2 test was of clinician time was spent on the guidance of both interventions (i.e., applied for categorical variables. FIBROWALK and MPP). An analysis of covariance (ANCOVA), considering baseline values as a covariate, was conducted to analyse between-group differences at 2.6. Study measures post-treatment in all study outcomes. The ANCOVA has shown greater power to discern changes than analyses of variance (ANOVA) in rand­ A sociodemographic and clinical ad-hoc questionnaire was used. It omised study designs (Van Breukelen, 2006). collected information about age, gender, educational level, employment Taking an Intention-To-Treat (ITT) approach as reference, all out­ situation, living arrangement (alone/accompanied), civil status, height comes were analyzed using Multiple Imputation (Jakobsen, Gluud, and current weight (for calculating body mass index), illness self- Wetterslev, & Winkel, 2017). Five imputations of all outcome variables perceived start/duration, incapacity certificate (indicating level of in­ were computed, from which pooled post-treatment means and standard capacity if affirmative), and diagnosis of chronic fatigue syndrome by a deviations were calculated. The pooling of ANCOVA statistics is not rheumatologist (yes/no). available in SPSS. Therefore, the tables report inferential statistics (F, p, 4 M. Serrat et al. Behaviour Research and Therapy 158 (2022) 104188 Cohen’s d) for the most “pessimistic” analytic scenario, i.e., the impu­ “non-responders” were evaluated with a Student’s t-test (for quantita­ tation iteration that yielded the highest p-value, to prevent an inflation tive variables) and χ2-test (for categorical variables). All statistical an­ of false positives (Type I error). In addition, a sensitivity analysis was alyses were computed with the SPSS v25. conducted with the complete-case sample. The effect size (Cohen’s d) for each pairwise comparison, using the pooled baseline SD to analyse the 3. Results differences in the baseline-post intervention mean values and correct these values for the estimated population, was also computed for the 3.1. Participant’s flow and treatment adherence complete-case sample (Morris, 2008). For the imputed dataset, the d was calculated by subtracting the means and dividing the results by the As shown in Fig. 1, a total of 387 patients with FM were assessed for pooled standard deviation. Effect sizes were considered small (d = .20), eligibility. Fifty-seven did not meet the eligibility criteria, and therefore, medium (d = 0.50), and large (d = 0.80) according to classical cut-offs a total of 330 patients were finally included and randomised [TAU (n = (Cohen, 1988). 110), TAU + FIBROWALK (n = 110) and TAU + MPP (n = 110)]. The A ≥ 20% reduction in the total FIQR score at post-treatment participants’ mean age was approximately 53 years old (SD = 9.11; compared to pre-treatment was considered a clinically relevant treat­ range: 20–77). The mean body mass index (BMI) of 27.27 kg/cm2 (SD = ment response (Bennett et al., 2009). This classification in responders vs 5.56) indicated that the subject group was overweight. The mean FM non-responders was used to compute the Number Needed to Treat duration was 15.6 years (SD = 9.12). Approximately 24% of the par­ (NNT) of each intervention arm. The NNT is an index aimed at make ticipants were employed, 57% married/in a stable relationship, 83% results from RCTs more meaningful to clinicians. It refers to the esti­ lived with someone, 60% reported having secondary education level or mated number of individuals who need to be treated with a novel pro­ higher, 70% reported some degree of disability, and 86% had a co­ posed treatment (i.e., FIBROWALK or MPP) instead of the usual care for morbid chronic fatigue syndrome diagnosis (Table 1). Retention rate one additional patient to benefit (i.e., vs. TAU or MPP). An NNT between was high in the three intervention arms (around 10% dropped out of 2 and 5 is indicative of a clinically effective treatment in pharmaceutical treatment in each arm). No differences were found in the retention rate research (Cook & Sackett, 1995). Furthermore, in order to identify at post-treatment (FIBROWALK: 90.9%; MPP: 89.1%; TAU: 90.9%; baseline characteristics potentially associated with being a “responder” χ2(2) = 0.277, p = .87). All participants in the FIBROWALK and MPP in each evaluated treatments, baseline differences among sociodemo­ arms attended all 12 sessions of the programs, watched the videos, and graphic and clinical variables between “responders” and completed the weekly questionnaires. Fig. 1. CONSORT Flow diagram of participants throughout the randomised controlled trial. 5 M. Serrat et al. Behaviour Research and Therapy 158 (2022) 104188 3.2. Baseline differences between study arms Table 1 Demographic and baseline clinical characteristics by treatment groups. There were no statistically significant differences between treatment TAU (n TAU + TAU + F/χ2 p arms in demographic or baseline clinical characteristics (see Table 1). = 110) FIBROWALK (n MPP (n = (df) = 110) 110) 3.3. Between-group differences in the primary and secondary outcomes Age (years), M ± 53.48 52.78 ± 8.64 52.54 ± .318 .73 SD ± 8.93 9.78 (2) 3.3.1. Primary outcome Women, n (%) 103 109 (99.1) 107 5.27 .07 Individuals allocated to both active treatment arms showed greater (96.7) (97.3) (2) reductions in FIQR scores when compared to those allocated to TAU only Civil Status, n 9.61 .14 (p < .001; FIBROWALK, d = 0.80; MPP, d = .53). No differences in FIQR (%) (6) scores were found between the FIBROWALK and the MPP groups (p = Single 24 22 (20.0) 13 (12.7) .163; d = 0.26). Mean differences and SDs between pre- and post- (21.8) treatment for each study arm are detailed in Table 2 (ITT approach). Married 52 62 (56.4) 73 (66.4) (47.3) Similar results were found in the complete-case sample (Table 3). Divorced 27 21 (19.1) 16 (14.5) (24.5) 3.4. Secondary outcomes Widow 7 (6.4) 5 (4.5) 7 (6.4) Not living Alone, 84 93 (84.5) 97 (88.2) 5.72 .06 Patients allocated to FIBROWALK showed greater reductions in n (%) (76.4) (2) perceived pain intensity, kinesiophobia, anxiety and depressive symp­ Educational 14.86 .14 toms and increased physical functioning compared to the TAU only Level, n (%) (10) group (all p < .001), with medium-to-large effect sizes (d = 0.51–1.48). Without Studies 3 (2.7) 2 (1.8) 0 (0.0) Similarly, significant treatment effects (p < .05) in favor of the MPP arm Primary 9 (8.2) 10 (9.2) 6 (5.5) were found when compared to TAU in perceived pain intensity (d = .39), Education not completed kinesiophobia (d = 1.13), and depressive symptoms (d = 0.37) (all p < Primary 40 28 (25.5) 25 (22.7) .05). No differences between MPP and TAU were found in the other Education (36.4) outcomes. When comparing FIBROWALK and MPP arms, statistically Secondary 31 47 (42.7) 54 (49.1) significant effects in favor of the former were found in pain intensity, Education (28.2) Higher Education 24 20 (18.2) 23 (20.9) depression, and physical functioning (all p < .05), with small-to-medium (21.8) effect sizes (d = 0.24-0.49). Other 3 (2.7) 3 (2.7) 2 (1.8) Similar results were found when looking at the complete-case data­ Employment 14.71 .40 set, except for the differences between FIBROWALK and MPP arms in Situation, n (14) anxiety and depressive symptoms. As shown in Table 3, FIBROWALK (%) was significantly more effective than MPP for reducing anxiety symp­ Housekeeper 13 10 (9.1) 9 (8.2) toms (p = .036, d = 0.50). In the case of depressive symptoms, the dif­ (11.8) ferences were marginally significant in favor of FIBROWALK (p = .053, Active 22 26 (23.6) 30 (27.3) d = 0.22). (20.0) On leave 22 25 (22.7) 24 (21.8) (20.0) 3.5. Baseline differences between “Responders” and “Non-Responders” Unemployed with 6 (5.5) 13 (11.8) 5 (4.5) to treatment allowance Unemployed 10 (9.1) 7 (6.4) 4 (3.6) without In the FIBROWALK arm, individuals classified as responders indi­ allowance cated less anxiety (p = .02), depressive symptoms (p = .02) and better Retired 15 10 (9.1) 10 (9.1) physical functioning (p = .03) prior to treatment compared to non- (13.6) responders. MPP responders were older (p = .05), men (100% men vs. Temporary work 12 8 (7.3) 10 (9.1) disability (10.9) 94% of women; p = .05), reported less pain (p < .001), had less func­ Other 10 (9.1) 11 (10.0) 18 (16.4) tional impairment (p = .03), and better physical functioning (p = .01) than “non-responders.” All details are shown in Table 4. Incapacity 4.382 .36 3.6. Number Needed to Treat (NNT) certificate, n (4) (%) Forty-two subjects (42%) in the FIBROWALK arm and 33 subjects in No 31 24 (21.8) 35 (31.8) the MPP arm (34%) showed a clinically significant improvement in their (28.2) FIQR total score at post-treatment (i.e., ≥20%) so were considered re­ Between 33% and 65 73 (66.4) 58 (52.7) 66% (59.1) sponders, whereas only four subjects (4%) from the TAU only arm More than 66% 14 13 (11.8) 17 (15.5) achieved the status of responder. The absolute risk reduction in the (12.7) FIBROWALK arm in comparison with TAU only was 38% (95% CI = BMI, M ± SD 27.62 27.31 ± 6.17 26.89 ± .477 .62 27.59–48.41%), with an NNT = 3 (95% CI = 2.1 to 3.6). The absolute ± 5.41 5.06 (2) risk reduction obtained in the MPP versus TAU only was 29.67% (95% ISPS, M ± SD 15.79 16.21 ± 9.24 14.80 ± .692 .50 CI = 19.56–39.79%), with an NNT = 4. The absolute risk reduction ± 9.12 8.72 (2) obtained in the FIBROWALK versus the MPP arm was 8.33% (95% CI = With CFS, n (%) 94 100 (90.9) 88 (80.0) 5.27 .07 − 5.13 to 21.78%) with an NNT = 13. As in this latter case, the 95%CI for (85.5) (2) the absolute risk reduction extended from a negative number (FIBRO­ FIQR, M ± SD 74.72 ± 14.71 .043 .96 WALK may not benefit) to a positive number (FIBROWALK may benefit), the NNT result had no interpretable meaning. (continued on next page) 6 M. Serrat et al. Behaviour Research and Therapy 158 (2022) 104188 Table 1 (continued ) reports inferential statistics (F, p, Cohen’s d) for the imputation iteration that yielded the highest p-value, to prevent an inflation of false positives (Type I error). 95%CI for the between-groups difference adjusted means at post are shown. TAU = Treatment-as-usual; MPP = Multicomponent Physiotherapeutic Program; FIQR: Revised Fibromyalgia Impact Questionnaire; TSK: Tampa Scale for Kinesiophobia; HADS; Hospital Anxiety and Note: Statistically significant effects are shown in bold (p ≦ 0.05). Pooled post-treatment means and standard deviations are shown. Bonferroni-adjusted post hoc tests were conducted for pairwise comparisons. The table TAU + FIBROWALK vs TAU + MPP TAU (n TAU + TAU + F/χ2 p (-1.09 to − .08) (-2.23 to − .02) = 110) FIBROWALK (n MPP (n = (df) (-8.03 to .88) (-2.67 to .86) (-1.87 to .16) (4.68–13.61) = 110) 110) (95% CI) 74.57 75.16 ± ± 15.63 16.00 Pain (VAS), M ± 7.99 ± 8.02 ± 1.28 8.11 ± .204 .82 <.001 SD 1.44 1.57 .017 .045 .163 .654 .128 p TSK, M ± SD 30.56 30.16 ± 7.98 31.67 ± 1.100 .33 ± 7.99 7.46 .26 .34 .27 .38 .24 .49 d HADS Anxiety, M 13.70 12.93 ± 4.42 13.69 ± 1.314 .27 ± SD ± 4.31 4.12 (-7.29 to 1.65) (-.62 to 1.35) (4.59–13.28) HADS 12.69 12.06 ± 4.38 12.01 ± .838 .43 (6.26–9.84) (.053–2.28) (.22–1.23) (95% CI) Depression, M ± 4.31 4.83 ± SD SF36-PF, M ± SD 32.59 35.14 ± 20.15 34.81 ± .565 .57 TAU vs TAU + MPP ± 17.36 20.42 <.001 <.001 1.000 .002 .037 .389 Note: TAU = Treatment-as-usual; MPP = Multicomponent Physiotherapeutic p Program; BMI: Body Mass Index; CFS: Chronic Fatigue Syndrome; FIQR: Revised Descriptive statistics and between-group analyses for primary and secondary outcomes from an ITT approach (with multiple imputation of missing data). Fibromyalgia Impact Questionnaire; HADS: Hospital Anxiety and Depression 1.13 .53 .39 .12 .37 .27 Scale; ISPS: Illness Self-Perceived Start; SF-PF: Physical Functioning component d of the 36-Item Short Form Survey; TSK: Tampa Scale for Kinesiophobia. (-16.44 to − 7.49) 4. Discussion (8.83–17.74) (7.47–11.05) (1.22–3.35) (.85–1.86) (.66–2.63) TAU vs TAU + FIBROWALK (95% CI) Both the video-based FIBROWALK and MPP multicomponent treat­ ments were found to be more efficacious than TAU only, with small-to- large clinical effects. The superiority of these two programs over TAU Depression Scale; ISPS: Illness Self-Perceived Start; SF-PF: Physical Functioning component of the 36-Item Short Form Survey. <.001 <.001 <.001 <.001 <.001 <.001 only was corroborated by the low NNT values. Furthermore, FIBRO­ WALK produced additional clinical benefits when compared to MPP. p Our findings provide additional evidence of the effectiveness of video- 1.48 .80 .76 .51 .63 .83 based FIBROWALK, which was initially obtained in a pilot study dur­ d ing the first lockdown due to COVID-19 pandemic in Spain (Serrat, <.001 <.001 <.001 <.001 <.001 Coll-Omaña et al., 2021) and confirmed existing evidence of the efficacy .001 of PNE combined with therapeutic exercise in people with FM (Bar­ p renengoa-Cuadra et al., 2021; Ceballos-Laita et al., 2020; Louw, Puen­ 27.58 20.97 90.08 13.38 22.68 tedura, et al., 2016). 7.75 F Interestingly, although both FIBROWALK and MPP were effective in improving the primary outcome of perceived functional impairment, TAU + MPP (n = 110) only FIBROWALK showed statistically significant effects on all the study outcomes. Though the MPP program was also effective in reducing 75.16 ± 16.00 65.84 ± 19.34 34.81 ± 20.42 35.22 ± 20.02 31.67 ± 7.46 24.40 ± 7.24 13.69 ± 4.12 13.11 ± 4.59 12.01 ± 4.83 11.36 ± 5.05 perceived pain intensity, kinesiophobia, and depressive symptoms it did 8.11 ± 1.57 7.43 ± 2.01 Mean (SD) not result in improved anxiety symptoms and perceived level of physical function compared to TAU only. Furthermore, though the effect sizes were small-to-medium, FIBROWALK achieved statistically larger im­ provements in the secondary outcomes of pain intensity, anxiety (only in TAU + FIBROWALK (n = 110) the complete-case dataset) and depressive symptoms and physical function compared to MPP. These findings suggest a broader and stronger therapeutic effect by combining psychological ingredients with physiotherapy interventions based on PNE and therapeutic exercise. These results are in line with other studies evaluating the effects of 74.72 ± 14.71 60.68 ± 20.56 35.14 ± 20.15 45.14 ± 20.80 30.16 ± 7.98 22.52 ± 6.55 12.93 ± 4.42 11.35 ± 4.74 12.06 ± 4.38 10.15 ± 4.93 8.02 ± 1.28 6.73 ± 2.12 physiotherapy plus psychological interventions compared with physio­ Mean (SD) therapy alone in other chronic pain samples (Wilson & Cramp, 2018). These findings are remarkably important, as they support the inclusion of evidence-based psychotherapeutic approaches in ongoing multicom­ ponent physiotherapy programs for people with FM. TAU (n = 110) 74.57 ± 15.63 74.92 ± 14.58 32.59 ± 17.36 30.47 ± 14.09 30.56 ± 7.99 32.11 ± 6.44 13.70 ± 4.31 13.66 ± 4.37 12.69 ± 4.31 13.12 ± 4.53 7.99 ± 1.44 8.12 ± 1.50 The efficacy of the two treatments, in part, rely on the shared com­ Mean (SD) ponents of PNE and therapeutic exercise. Many studies have separately supported the efficacy of both PNE and therapeutic exercise (e.g., adapted aerobic and muscle strengthening exercises) in reducing pain, HADS Depression affective symptoms, kinesiophobia, and perceived disability and in Post-Treatment Post-Treatment Post-Treatment Post-Treatment Post-Treatment Post-Treatment HADS Anxiety improving global well-being and health-related quality of life in people Pain (VAS) with musculoskeletal pain (Sosa-Reina et al., 2017; Watson et al., 2019). Baseline Baseline Baseline Baseline Baseline Baseline It is known that PNE and therapeutic exercise can be even more effective Table 2 SF-PF FIQR TSK when combined (Louw, Zimney, Puentedura, & Diener, 2016; Malfliet 7 M. Serrat et al. Behaviour Research and Therapy 158 (2022) 104188 et al., 2017). Furthermore, FIBROWALK and MPP shared other applied to correct for multiple comparisons, all significant effects remained significant. 95%CI for the between-groups difference adjusted means at post are shown. TAU = Treatment-as-usual; MPP = Multicomponent Note: Statistically significant effects are shown in bold (p ≦ 0.05). Unadjusted means are shown. Bonferroni-adjusted post hoc tests were conducted for pairwise comparisons. When the Benjamini–Hochberg correction was Physiotherapy Program; FIQR: Revised Fibromyalgia Impact Questionnaire; HADS: Hospital Anxiety and Depression Scale; ISPS: Illness Self-Perceived Start; SF-PF: Physical Functioning component of the 36-Item Short self-management and patient education components, which were found TAU + FIBROWALK vs TAU + MPP (-1.12 to − .05) (-1.03 to 2.74) in a recent systematic review in FM to be effective in improving pain (-.42 to 8.85) (-.01 to 2.28) (4.05–13.42) intensity, fatigue, sleep quality, depression, anxiety, functional ability, (.05–2.16) (95% CI) cognitive impairment, and quality of life (Gómez-de-Regil, 2021). While superior improvements in anxiety and depressive symptoms were expected outcomes for the FIBROWALK arm, participants allocated to this intervention also showed greater pain ameliorations and physical <.001 .025 .036 .088 .829 .053 functioning when compared to those allocated to MPP. Similar results p have also been found in other studies assessing the effects of CBT or .26 .40 .21 .50 .22 .42 mindfulness-based interventions in subjects with FM (Bennett & Nelson, d 2006; Kundakci et al., 2021; Williams et al., 2002). Moreover, larger (-1.31 to − .25) improvements in physical function after multidisciplinary interventions, (-.46 to 1.65) (-.89 to 8.49) (5.09–14.36) (6.44–10.20) including both psychotherapeutic and physiotherapeutic components (.02–2.31) (95% CI) compared to physiotherapy interventions alone were also reported in a systematic review and meta-analysis including different chronic pain samples (Wilson & Cramp, 2018). In this regard, it is known that patients TAU vs TAU + MPP suffering from chronic pain tend to exhibit maladaptive beliefs <.001 <.001 .002 .045 .521 .156 regarding physical exercise (Harding & Williams, 1995), which can lead p to a sedentary lifestyle and non-compliance with physical therapy rec­ − 1.39 ommendations (Dysvik, Vinsnes, & Eikeland, 2004). Avoidance of − .62 − .33 − .26 .54 .61 physical activity is often a barrier to recovery and can contribute to d reduced physical function, deconditioning, and increased pain. The (-1.90 to − .84) psychological components included in FIBROWALK were aimed at (9.33–18.55) (7.30–11.04) (7.87–17.20) (1.16–3.44) helping patients overcome such barriers by modifying maladaptive pain (.65–2.75) (95% CI) TAU vs TAU + FIBROWALK beliefs and cognitive biases and fostering adaptive emotional regulation in order to reduce pain catastrophizing, increase psychological flexi­ bility, and promote positive behavioural changes. Addressing these <.001 <.001 <.001 <.001 <.001 <.001 barriers to function are essential steps for escaping from the vicious circle of fear and avoidance of physical activity in musculoskeletal pain p (Vlaeyen, Crombez, & Linton, 2016; Wright & Gatchel, 2002). Similarly, − 1.14 mindfulness can play an important role in breaking this vicious circle by − .92 − .33 − .50 1.01 .61 reducing negative rumination, increasing pain acceptance, and d Descriptive statistics and between-group analyses for primary and secondary outcomes (only with completers). improving one’s ability to stay focused on the present moment with a <.001 <.001 <.001 <.001 <.001 <.001 non-judgemental attitude (Curtin & Norris, 2017; McCracken & Keogh, P 2009; Pérez-Aranda, Feliu-Soler, et al., 2019). Both cognitive restruc­ turing and mindfulness, combined with PNE, can contribute to reduce 27.84 19.38 85.17 11.78 22.00 7.87 fear of pain and fear of movement (Jay et al., 2016). In this way, CBT, F Mindfulness, therapeutic exercise and PNE might present a synergistic effect (Heller et al., 2021) in which all components have a greater effect TAU + MPP (n = 98) when combined than the sum of their separate effects. Furthermore, 74.77 ± 16.64 65.28 ± 19.80 11.20 ± 5.103 35.92 ± 20.39 given the known bidirectional relationship between pain-related distress 31.67 ± 7.19 22.29 ± 7.35 13.51 ± 4.16 12.93 ± 4.60 11.87 ± 4.67 8.08 ± 1.62 7.39 ± 2.08 35 ± 21.26 and physical function (e.g., Stegenga et al., 2012; Talaei-Khoei et al., Mean (SD) 2018; Wegener et al., 2011), the additional CBT and mindfulness ap­ proaches for reducing pain-related distress in FIBROWALK may have contributed to the stronger therapeutic effects compared to MPP and TAU only. TAU + FIBROWALK (n = 100) When looking specifically at the impact on kinesiophobia, both active groups showed similar improvements (large effect sizes) compared to TAU. In this regard, adding CBT and mindfulness training did not increase the effects of the MPP on this variable, which probably 74.26 ± 14.91 60.66 ± 20.93 35.15 ± 20.46 44.75 ± 21.09 Form Survey; TSK: Tampa Scale for Kinesiophobia. 29.73 ± 8.02 22.43 ± 6.64 12.80 ± 4.53 11.27 ± 4.85 12.07 ± 4.54 10.23 ± 5.01 reached a therapeutic ceiling. Previous research has suggested that 7.99 ± 1.27 6.73 ± 2.16 Mean (SD) changes in cognitive biases and behavioural factors in chronic pain conditions might not occur exclusively by means of psychological ap­ proaches but also by providing subjects with comprehensive informa­ tion about the biopsychosocial essence of chronic pain as is done in PNE TAU (n = 100) 74.12 ± 15.92 74.49 ± 13.93 32.80 ± 17.35 30.70 ± 13.74 30.43 ± 7.99 31.96 ± 6.31 13.43 ± 4.26 13.47 ± 4.33 12.74 ± 4.41 13.05 ± 4.55 (Burns, Van Dyke, Newman, Morais, & Thorn, 2020). PNE is aimed at 7.97 ± 1.45 8.08 ± 1.43 Mean (SD) reconceptualizing pain in order to break the cycle of fear of movement and avoidance. Previous studies have reported that PNE is high effec­ tivity in reducing kinesiophobia in FM and other musculoskeletal pain conditions (Louw, Diener, Butler, & Puentedura, 2011; Luque-Suarez, HADS Depression Post-Treatment Post-Treatment Post-Treatment Post-Treatment Post-Treatment Post-Treatment Martinez-Calderon, & Falla, 2019; Siddall et al., 2022; Watson et al., HADS Anxiety 2019). Pain (VAS) Baseline Baseline Baseline Baseline Baseline Baseline Although both FIBROWALK and MPP were clearly superior to TAU Table 3 SF-PF alone, it is important to highlight that only 42% and 34% of the par­ FIQR TSK ticipants, respectively, showed a clinically significant improvement (i.e., 8 M. Serrat et al. Behaviour Research and Therapy 158 (2022) 104188 Table 4 Baseline differences between responders (FIQR≧20%) and non-responders from the FIBROWALK and MPP. FIBROWALK (n = MPP (n = 98) 100) Non-Responders (n = Responders (n = 42) t/x2 p Non-Responders (n = Responders (n = t/x2 p 58) 65) 33) Age (years), M ± SD 52.59 ± 7.84 54.40 ± 9.28 − 1.031 .306 51.42 ± 9.81 55.12 ± 7.78 − 2.035 .045 Women, n (%) 58 (100.0) 41 (97.6) 1.395 .238 65 (100) 31 (93.9) 4.021 .045 Civil Status, n (%) 2.326 .508 .109 .991 Single 14 (24.1) 8 (19.0) 8 (12.3) 4 (12.1) Married 28 (48.3) 26 (61.9) 43 (66.2) 22 (66.7) Divorced 12 (20.7) 7 (16.7) 9 (13.8) 5 (15.2) Widow 4 (6.9) 1 (2.4) 5 (7.7) 2 (6.1) Not living Alone, n (%) 50 (86.2) 34 (81.0) .500 .479 60 (92.3) 27 (81.8) 2.417 .120 Educational Level, n (%) 6.977 .222 1.996 .736 Without Stydies 2 (3.4) 0 (0.0) Primary Education not 8 (13.8) 1 (2.4) 4 (6.2) 1 (3.0) completed Primary Education 13 (22.4) 14 (33.3) 14 (21.5) 8 (24.2) Secondary Education 25 (43.1) 19 (45.2) 34 (52.3) 15 (45.5) Higher Education 9 (15.5) 8 (19.0) 12 (18.5) 9 (27.3) Other 1 (1.7) 0 (0.0) 1 (1.5) 0(0.0) Employment Situation, n (%) 4.279 .747 6.002 .539 Housekeeper 4 (6.9) 3 (7.1) 5 (7.7) 3 (9.1) Active 13 (22.4) 9 (21.4) 18 (27.7) 10 (30.3) On leave 16 (27.6) 8 (19.0) 18 (27.7) 5 (15.2) Unemployed with allowance 8 (13.8) 5 (11.9) 4 (6.2) 1 (3.0) Unemployed without 4 (6.9) 3 (7.1) 1 (1.5) 1 (3.0) allowance Retired 3 (5.2) 7 (16.7) 3 (4.6) 5 (15.2) Temporary work disability 4 (6.9) 2 (4.8) 7 (10.8) 2 (6.1) Other 6 (10.3) 5 (11.9) 9 (13.8) 6 (18.2) Incapacity certificate, n (%) 6.665 .155 1.220 .748 No 12 (20.7) 8 (19.0) 19 (29.2) 12 (36.4) Between 33% and 66% 40 (69.0) 23 (54.8) 32 (49.2) 15 (45.5) More than 66% 5 (8.6) 5 (11.9) 9 (13.8) 5 (15.2) BMI, M ± SD 27.28 ± 5.86 27.77 ± 6.88 − .371 .711 26.84 ± 5.38 27.11 ± 4.97 − .248 .805 ISPS, years, M ± SD 16.62 ± 10.14 15.48 ± 8.09 .627 .532 14.83 ± 8.41 14.27 ± 9.09 .294 .769 With CFS, n (%) 55 (94.8) 37 (88.1) 1.500 .221 53 (81.5) 25 (75.8) .450 .502 FIQR, M ± SD 75.59 ± 15.34 72.43 ± 14.28 1.056 .294 77.46 ± 15.48 69.47 ± 17.79 2.193 .032 Pain (VAS), M ± SD 8.09 ± 1.27 7.86 ± 1.26 .891 .375 8.46 ± 1.44 7.33 ± 1.73 3.429 .001 TSK, M ± SD 30.07 ± 7.55 20.26 ± 8.70 .484 .630 31.92 ± 6.89 31.18 ± 7.84 .460 .647 HADS Anxiety, M ± SD 13.71 ± 4.01 11.55 ± 4.95 2.328 .023 14.26 ± 3.79 12.03 ± 4.52 2.436 .018 HADS Depression, M ± SD 12.98 ± 4.05 10.81 ± 4.91 2.349 .021 12.42 ± 5.00 10.79 ± 3.76 1.646 .103 SF36-PF, M ± SD 31.29 ± 18.79 40.47 ± 21.66 − 2.210 .030 31.15 ± 21.02 42.58 ± 19.93 − 2.632 .011 Note: Statistically significant effects appear in bold (p ≦ 0.05). MPP = Multicomponent Physiotherapeutic Program; BMI: Body Mass Index; CFS: Chronic Fatigue Syndrome; FIQR: Revised Fibromyalgia Impact Questionnaire; TSK: Tampa Scale for Kinesiophobia; HADS: Hospital Anxiety and Depression Scale; ISPS: Illness Self- Perceived Start; SF-PF: Physical Functioning component of the 36-Item Short Form Survey. 20% between pre- and post-treatment) in the primary outcome measure Furthermore, these telemedicine programs may help reduce healthcare of perceived functional impairment, as determined by FIQR scores. costs and decongest health system services which are experiencing huge Though FIBROWALK in the present study yielded a higher rate of re­ workload burdens as a result of the current COVID-19 pandemic sponders (43%) than the initial pilot RCT (30%), which was conducted (Moman et al., 2019). during the Spanish lockdown (Serrat, Coll-Omaña, et al., 2021), there is Although comparisons in effectiveness between the virtual and face- room for considerable improvement. Moreover, greater clinical effects to-face formats of FIBROWALK should be evaluated in future RCTs, in FIQR scores (Cohen’s d of 0.83 vs 1.13; NNT = 3 vs 2) and a larger many factors may contribute to these apparent differences, including the proportion of treatment “responders” were found in the face-to-face feeling of belonging to a group and having regular contact with a ther­ FIBROWALK format (Serrat, Sanabria-Mazo, et al., 2021) compared to apist, which both have potentially therapeutic benefits. Furthermore, we the video-based version in the present study (42% vs 51.85%). It is also cannot rule out that our results would have been better in a patient important to note that, although online approaches may be less effective sample with less severe symptoms. In this regard, compared to non- than equivalent face-to-face options, these video-based programs are responders in the present study, the responders reported lower pre- highly scalable and have the potential to provide treatment availability treatment symptom severity. In general, the patients in our sample re­ for FM patients who are unable to attend face-to-face sessions. ported a relatively high degree of pre-treatment functional impairment, 9 M. Serrat et al. Behaviour Research and Therapy 158 (2022) 104188 low degree of perceived physical function, high perceived pain intensity initially being told about the virtual nature of the intervention, which and a moderate degree of depressive and anxiety symptomatology. may have undermined the generalizability of our findings. Finally, this Future studies should evaluate if additional treatment time or tailored trial was conducted under de COVID-19 pandemic context and after adaptations of FIBROWALK (e.g., adding individual therapy or extra termination of national lockdowns. Given the well-known negative ef­ CBT virtual sessions for those individuals scoring high in anxiety and/or fects of these circumstances on mental health and treatment adherence depression) may work better for those patients with a higher risk of non- (e.g., López-Medina et al., 2021), further studies conducted beyond responsiveness. In this regard, evidence-based care has started to move current pandemic context should be done to evaluate the generaliz­ toward process-based therapies to target core mediators and moderators ability of our findings. based on testable theories, to identify what treatments are most effec­ tive, for whom, why and under what set of circumstances (Hofmann & 5. Conclusions Hayes, 2019; McCracken, 2020). This change of perspective from “one size fits all” to more individualised treatment may better suit the high This study showed that two video-based multicomponent treatments level of complexity that chronic pain conditions, and particularly FM, including PNE, therapeutic exercise and self-management patient edu­ present. cation, were clinically effective in improving functional disability, pain Finally, FIBROWALK and MPP showed a relatively low attrition rate and kinesiophobia compared to TAU only for people with FM. (around 10%). This low rate of dropouts supports the feasibility of these Furthermore, FIBROWALK, which combined all therapeutic components virtual interventions. A range between 4% and 54% of attrition has been of MPP with cognitive restructuring and mindfulness training, was more found with other online interventions in patients with chronic pain effective in reducing anxiety, depressive symptoms and in improving (Buhrman, Gordh, & Andersson, 2016). The attrition rate in FIBRO­ physical function than MPP or TAU only. The results of this RCT support WALK was also lower than in the pilot RCT conducted during the the clinical effectiveness of both video-based treatments over usual care COVID-19 outbreak (38.7%; Serrat, Coll-Omaña, et al., 2021) and even in FM and provide more scientific evidence regarding the increased lower than the reported in the face-to-face version of the program (9% vs benefits of combining physical therapy and psychological techniques in 24%) (Serrat, Sanabria-Mazo, et al., 2021). This finding may suggest a the management of this highly prevalent and limiting disease. superior ability of the virtual format of the FIBROWALK for engaging participants who were not able to attend a 12-week face-to-face inter­ Funding vention. The increased adherence and low attrition rate of participants in the present study could have been due to the high flexibility of the This research was funded by the Vall d’Hebron Institute of Research. video-based format, participation through the hospital system from This study has also been funded by the Ministry of Science and Inno­ which they were receiving TAU care, the emphasis at the beginning of vation (PID2020-117667RA-I00) and has been co-financed with Euro­ the study about the importance of actively participating in the inter­ pean Union ERDF funds. The authors declare no conflict of interest. The vention, and therapist support during the program. Results from the funding sources had no influence on the design of the study, data present study suggest that the virtual interventions of FIBROWALK and collection, analysis, writing of the manuscript, or on the decision to MPP can be effective therapeutic alternatives to classical face-to-face submit the paper for publication. treatments in times of pandemics and beyond when it comes to spe­ cific logistic barriers, such as timing, difficulties in access to treatment in CRediT authorship contribution statement remote areas, or other perceived barriers, such as individual’s fatigue or family conciliation issues. Mayte Serrat: Conceptualization, Methodology, Resources, Soft­ This RCT had several strengths, such as the inclusion of two inno­ ware, Data curation, Validation, Formal analysis, Investigation, Writing vative video-based active treatments that were structurally equivalent, – original draft, Writing – review & editing, Supervision, Project the relatively large sample size and the reduced number of dropouts. administration, Funding acquisition. Klara Albajes: Conceptualization, However, there were several limitations. First, comparisons between the Methodology, Resources, Software, Data curation, Validation, Formal two intervention groups (FIBROWALK vs MPP) may have been under­ analysis, Writing – original draft, Writing – review & editing, Supervi­ powered. Second, this study was carried out in daily clinical practice in a sion. Jaime Navarrete: Formal analysis, Writing – review & editing. specialised tertiary care hospital. Therefore, stricter eligibility criteria Miriam Almirall: Writing – review & editing, Supervision. Enrique could not be applied. Subjects with certified disability were included in Lluch Girbés: Writing – review & editing. Randy Neblett: Writing – our sample. The sample was composed of people with FM with high review & editing. Juan V. Luciano: Conceptualization, Writing – review impact on daily functioning and relatively long duration of the disease. & editing, Supervision. Jenny Moix: Writing – review & editing, Su­ Future studies could explore the role of multicomponent interventions in pervision. Albert Feliu-Soler: Conceptualization, Methodology, Re­ other settings (e.g. primary care) including less severe patients. Third, sources, Software, Data curation, Validation, Formal analysis, Writing – no long-term follow-ups were done, due the fact that the present study original draft, Writing – review & editing, Supervision, Project admin­ was carried out within usual clinical practice. Future studies should istration, Funding acquisition. include long-term follow-ups for assessing the stability of the observed clinical effects. Fourth, it cannot be confirmed that all subjects viewed all the videos and performed all the homework, even though they re­ Declaration of competing interest ported compliance in a weekly questionnaire format. Fifth, all outcome data were patient-reported. No objective functional data were The authors declare no conflict of interest. The funders had no role in measured. Though it is common to use patient-reported data to evaluate the design of the study; in the collection, analyses, or interpretation of FM symptom domains (Outcome Measures in Rheumatology Clinical data; in the writing of the manuscript, or in the decision to publish the Trials; Mease et al., 2009), future studies should include complementary results. objective measures. Future studies should also include weekly patient-reported state measures to examine the evolution of participants Acknowledgements throughout the study instead of only at the end of the intervention (e.g., Navarrete, García-Salvador, Cebolla, & Baños, 2022). Sixth, future J.V.L. had a “Miguel Servet” research contract from the ISCIII studies should evaluate potential sampling bias, which are inherent to (CPII19/00003) when the study was conducted. A.F.-S. is a Serra Húnter any study, including online interventions. Participants with a perceived Fellow (UAB-LE-8015). J.N. has a research contract from the Institute of low digital competency may have been self-excluded themselves when Health Carlos III (ISCIII; ICI20/00080). 10 M. Serrat et al. Behaviour Research and Therapy 158 (2022) 104188 Appendix A. Supplementary data De Miquel, C. A., Campayo, J., Flórez, M. T., Arguelles, J. M., Tarrio, E. B., Montoya, M. G., et al. (2010). Interdisciplinary consensus document for the treatment of fibromyalgia. Actas Espanolas de Psiquiatria, 38(2), 108–120. Supplementary data to this article can be found online at https://doi. Dysvik, E., Vinsnes, A. G., & Eikeland, O. J. (2004). The effectiveness of a org/10.1016/j.brat.2022.104188. multidisciplinary pain management programme managing chronic pain. International Journal of Nursing Practice, 10(5), 224–234. https://doi.org/10.1111/ j.1440-172X.2004.00485.x References Etzelmueller, A., Vis, C., Karyotaki, E., Baumeister, H., Titov, N., Berking, M., et al. (2020). Effects of internet-based cognitive behavioral therapy in routine care for Albajes, K., & Moix, J. (2021). Psychological interventions in fibromyalgia: An updated adults in treatment for depression and anxiety: Systematic review and meta-analysis. systematic review. Mediterranean Journal of Clinical Psychology, 9(1). https://doi. Journal of Medical Internet Research, 22(8), Article e18100. https://doi.org/10.2196/ org/10.6092/2282-1619/mjcp-2759 18100 Alonso, J., Prieto, L., & Antó, J. M. (1995). La versión española del SF-36 health survey Galvez-Sánchez, C. M., Duschek, S., & Reyes Del Paso, G. A. (2019). Psychological impact (Cuestionario de Salud SF-36): Un instrumento para la medida de los resultados of fibromyalgia: Current perspectives. Psychology Research and Behavior Management, clínicos [the Spanish version of the SF-36 health survey (the SF-36 health 12, 117–127. https://doi.org/10.2147/PRBM.S178240 questionnaire): An instrument for measuring clinical results]. Medicina Clínica, 104 Glombiewski, J. A., Sawyer, A. T., Gutermann, J., Koenig, K., Rief, W., & Hofmann, S. G. (20), 771–776. PMID: 7783470. (2010). Psychological treatments for fibromyalgia: A meta-analysis. Pain, 151(2), Aman, M. M., Jason Yong, R., Kaye, A. D., & Urman, R. D. (2018). Evidence-based non- 280–295. https://doi.org/10.1016/j.pain.2010.06.011 pharmacological therapies for fibromyalgia. Current Pain and Headache Reports, 22 Gómez-de-Regil, L. (2021). Psychoeducation for patients with fibromyalgia: A systematic (5), 1–5. review. Healthcare (Basel, Switzerland), 9(6), 737. https://doi.org/10.3390/ Amer-Cuenca, J. J., Pecos-Martín, D., Martínez-Merinero, P., Lluch Girbés, E., Nijs, J., healthcare9060737 Meeus, M., et al. (2020). How much is needed? Comparison of the effectiveness of Gómez-Pérez, L., López-Martínez, A. E., & Ruiz-Párraga, G. T. (2011). Psychometric different pain education dosages in patients with fibromyalgia. Pain Medicine, 21(4), properties of the Spanish version of the Tampa scale for kinesiophobia (TSK). The 782–793. https://doi.org/10.1093/pm/pnz069 Journal of Pain, 12(4), 425–435. https://doi.org/10.1016/j.jpain.2010.08.004 Andersson, G. (2018). Internet interventions: Past, present and future. Internet Harding, V., & Williams, A. C. (1995). Extending physiotherapy skills using a interventions, 12, 181–188. psychological approach: Cognitive-behavioural management of chronic pain. Andersson, G., & Titov, N. (2014). Advantages and limitations of Internet-based Physiotherapy, 81, 681–688. https://doi.org/10.1016/S0031-9406(05)66622-9 interventions for common mental disorders. World Psychiatry, 13(1), 4–11. Haugmark, T., Hagen, K. B., Smedslund, G., & Zangi, H. A. (2019). Mindfulness- and Barrenengoa-Cuadra, M. J., Muñoa-Capron-Manieux, M., Fernández-Luco, M., Angón- acceptance-based interventions for patients with fibromyalgia - a systematic review Puras, L.Á., Romón-Gómez, A. J., Azkuenaga, M., et al., FIMIDOC Working Group and meta-analyses. PLoS One, 14(9), Article e0221897. https://doi.org/10.1371/ researchers. (2021). Effectiveness of a structured group intervention based on pain journal.pone.0221897 neuroscience education for patients with fibromyalgia in primary care: A multicentre Häuser, W., Ablin, J., Fitzcharles, M. A., Littlejohn, G., Luciano, J. V., Usui, C., et al. randomized open-label controlled trial. European Journal of Pain, 25(5), 1137–1149. (2015). Fibromyalgia. Nature Reviews Disease Primers, 1(1), 1–16. https://doi.org/ https://doi.org/10.1002/ejp.1738 10.1038/nrdp.2015.22 Bennett, R. M., Friend, R., Jones, K. D., Ward, R., Han, B. K., & Ross, R. L. (2009). The Häuser, W., Bernardy, K., Arnold, B., Offenbächer, M., & Schiltenwolf, M. (2009). revised fibromyalgia impact questionnaire (FIQR): Validation and psychometric Efficacy of multicomponent treatment in fibromyalgia syndrome: A meta-analysis of properties. Arthritis Research and Therapy, 11(4), R120. https://doi.org/10.1186/ randomized controlled clinical trials. Arthritis & Rheumatism, 61(2), 216–224. ar2783 https://doi.org/10.1002/art.24276 Bennett, R., & Nelson, D. (2006). Cognitive behavioral therapy for fibromyalgia. Nature Heller, H. L., Borges, A. R., Franco, L. O. A., De Oliveira Aucelio, J. P., Vargas, M. I. A., Clinical Practice Rheumatology, 2(8), 416–424. https://doi.org/10.1038/ Lorga, R. N., et al. (2021). Role of cognitive behavioral therapy in fibromyalgia: A ncprheum0245 systematic review. Open Journal of Rheumatology and Autoimmune Diseases, 11, Bernardy, K., Klose, P., Welsch, P., & Häuser, W. (2018). Efficacy, acceptability and 169–187. https://doi.org/10.4236/ojra.2021.114018 safety of cognitive behavioural therapies in fibromyalgia syndrome - a systematic Hofmann, S. G., & Hayes, S. C. (2019). The future of intervention science: Process-based review and meta-analysis of randomized controlled trials. European Journal of Pain, therapy. Clinical Psychological Science : A Journal of the Association for Psychological 22(2), 242–260. https://doi.org/10.1002/ejp.1121 Science, 7(1), 37–50. https://doi.org/10.1177/2167702618772296 Bernardy, K., Klose, P., Welsch, P., & Häuser, W. (2019). Efficacy, acceptability and Jakobsen, J. C., Gluud, C., Wetterslev, J., & Winkel, P. (2017). When and how should safety of internet-delivered psychological therapies for fibromyalgia syndrome: A multiple imputation be used for handling missing data in randomised clinical trials–a systematic review and meta-analysis of randomized controlled trials. European practical guide with flowcharts. BMC Medical Research Methodology, 17(1), 1–10. Journal of Pain, 23(1), 3–14. https://doi.org/10.1002/ejp.1284 Jay, K., Brandt, M., Jakobsen, M. D., Sundstrup, E., Berthelsen, K. G., Schraefel, M., et al. Buhrman, M., Gordh, T., & Andersson, G. (2016). Internet interventions for chronic pain (2016). Ten weeks of physical-cognitive-mindfulness training reduces fear- including headache: A systematic review. Internet interventions, 4, 17–34. https://doi. avoidance beliefs about work-related activity: Randomized controlled trial. Medicine, org/10.1016/j.invent.2015.12.001 95(34), e3945. https://doi.org/10.1097/MD.0000000000003945 Burns, J. W., Van Dyke, B. P., Newman, A. K., Morais, C. A., & Thorn, B. E. (2020). Kabat-Zinn, J. (2013). Full catastrophe living, revised edition: How to cope with stress, pain Cognitive behavioral therapy (CBT) and pain education for people with chronic pain: and illness using mindfulness meditation (Paperback UK). Tests of treatment mechanisms. Journal of Consulting and Clinical Psychology, 88(11), Kamper, S. J., Apeldoorn, A. T., Chiarotto, A., Smeets, R. J., Ostelo, R. W., Guzman, J., 1008–1018. https://doi.org/10.1037/ccp0000612 et al. (2015). Multidisciplinary biopsychosocial rehabilitation for chronic low back Camerini, L., Camerini, A. L., & Schulz, P. J. (2013). Do participation and personalization pain: Cochrane systematic review and meta-analysis. BMJ, 350, h444. https://doi. matter? A model-driven evaluation of an internet-based patient education org/10.1136/bmj.h444 intervention for fibromyalgia patients. Patient Education and Counseling, 92(2), Kleykamp, B. A., Ferguson, M. C., McNicol, E., Bixho, I., Arnold, L. M., Edwards, R. R., 229–234. https://doi.org/10.1016/j.pec.2013.04.007 et al. (2021). The prevalence of psychiatric and chronic pain comorbidities in Ceballos-Laita, L., Mingo-Gómez, M. T., Navas-Cámara, F., Estébanez-de-Miguel, E., fibromyalgia: An ACTION systematic review. Seminars in Arthritis and Rheumatism, Caudevilla-Polo, S., Verde-Rello, Z., et al. (2020). Therapeutic exercise and pain 51(1), 166–174. https://doi.org/10.1016/j.semarthrit.2020.10.006 neurophysiology education in female patients with fibromyalgia syndrome: A Kundakci, B., Kaur, J., Goh, S. L., Hall, M., Doherty, M., Zhang, W., et al. (2021). Efficacy feasibility study. Journal of Clinical Medicine, 9(11), 3564. https://doi.org/10.3390/ of nonpharmacological interventions for individual features of fibromyalgia: A jcm9113564 systematic review and meta-analysis of randomised controlled trials. Pain. https:// Cohen, J. (1988). Statistical power analysis for the behavioral sciences (No. 300.72 C6). New doi.org/10.1097/j.pain.0000000000002500, 10.1097/j.pain.0000000000002500. York, NY: Routledge Academic. Advance online publication. Conversano, C., & Di Giuseppe, M. (2021). Psychological factors as determinants of Lichtenstein, A., Tiosano, S., & Amital, H. (2018). The complexities of fibromyalgia and chronic conditions: Clinical and psychodynamic advances. Frontiers in Psychology, its comorbidities. Current Opinion in Rheumatology, 30(1), 94–100. https://doi.org/ 12, Article 635708. https://doi.org/10.3389/fpsyg.2021.635708 10.1097/BOR.0000000000000464 Cook, R. J., & Sackett, D. L. (1995). The number needed to treat: A clinically useful López-Medina, C., Ladehesa-Pineda, L., Gómez-García, I., Puche-Larrubia, M.Á., Sequí- measure of treatment effect. BMJ, 310(6977), 452–454. https://doi.org/10.1136/ Sabater, J. M., Armenteros-Ortiz, P., et al. (2021). Treatment adherence during the bmj.310.6977.452 COVID-19 pandemic and the impact of confinement on disease activity and Cunningham, N. R., & Kashikar-Zuck, S. (2013). Nonpharmacological treatment of pain emotional status: A survey in 644 rheumatic patients. Joint Bone Spine, 88(2), Article in rheumatic diseases and other musculoskeletal pain conditions. Current 105085. https://doi.org/10.1016/j.jbspin.2020.105085 Rheumatology Reports, 15(2), 306. https://doi.org/10.1007/s11926-012-0306-y Louw, A., Diener, I., Butler, D. S., & Puentedura, E. J. (2011). The effect of neuroscience Curtin, K. B., & Norris, D. (2017). The relationship between chronic musculoskeletal education on pain, disability, anxiety, and stress in chronic musculoskeletal pain. pain, anxiety and mindfulness: Adjustments to the Fear-Avoidance Model of Chronic Archives of Physical Medicine and Rehabilitation, 92(12), 2041–2056. https://doi.org/ Pain. Scandinavian journal of pain, 17, 156–166. https://doi.org/10.1016/j. 10.1016/j.apmr.2011.07.198 sjpain.2017.08.006 Louw, A., Puentedura, E. J., Zimney, K., & Schmidt, S. (2016). Know pain, know gain? A Davis, M. C., & Zautra, A. J. (2013). An online mindfulness intervention targeting perspective on pain neuroscience education in physical therapy. Journal of socioemotional regulation in fibromyalgia: Results of a randomized controlled trial. Orthopaedic & Sports Physical Therapy, 46(3), 131–134. https://doi.org/10.2519/ Annals of Behavioral Medicine : A Publication of the Society of Behavioral Medicine, 46 jospt.2016.0602 (3), 273–284. https://doi.org/10.1007/s12160-013-9513-7 Louw, A., Zimney, K., Puentedura, E. J., & Diener, I. (2016). The efficacy of pain neuroscience education on musculoskeletal pain: A systematic review of the 11 M. Serrat et al. Behaviour Research and Therapy 158 (2022) 104188 literature. Physiotherapy: Theory and Practice, 32(5), 332–355. https://doi.org/ care for fibromyalgia: The EUDAIMON study. Pain, 160(11), 2508–2523. https:// 10.1080/09593985.2016.1194646 doi.org/10.1097/j.pain.0000000000001655 Luciano, J. V., Aguado, J., Serrano-Blanco, A., Calandre, E. P., & Rodriguez-Lopez, C. M. Perrot, S., & Russell, I. J. (2014). More ubiquitous effects from non-pharmacologic than (2013). Dimensionality, reliability, and validity of the revised fibromyalgia impact from pharmacologic treatments for fibromyalgia syndrome: A meta-analysis questionnaire in two Spanish samples. Arthritis Care & Research, 65(10), 1682–1689. examining six core symptoms. European Journal of Pain, 18(8), 1067–1080. https:// https://doi.org/10.1002/acr.22034 doi.org/10.1002/ejp.564 Luciano, J. V., Barrada, J. R., Aguado, J., Osma, J., & García-Campayo, J. (2014). Rivera, J., Alegre, C., Ballina, F. J., Carbonell, J., Carmona, L., Castel, B., et al. (2006). Bifactor analysis and construct validity of the HADS: A cross-sectional and Documento de consenso de la Sociedad Española de Reumatología sobre la longitudinal study in fibromyalgia patients. Psychological Assessment, 26(2), fibromialgia. Reumatología Clínica, 2(Suppl 1). S55–S66. 10.1016. 395–406. https://doi.org/10.1037/a0035284 Serrat, M., Almirall, M., Musté, M., Sanabria-Mazo, J. P., Feliu-Soler, A., Méndez- Luque-Suarez, A., Martinez-Calderon, J., & Falla, D. (2019). Role of kinesiophobia on Ulrich, J. L., et al. (2020). Effectiveness of a multicomponent treatment for pain, disability and quality of life in people suffering from chronic musculoskeletal fibromyalgia based on pain neuroscience education, exercise therapy, psychological pain: A systematic review. British Journal of Sports Medicine, 53(9), 554–559. https:// support, and nature exposure (NAT-FM): A pragmatic randomized controlled trial. doi.org/10.1136/bjsports-2017-098673 Journal of Clinical Medicine, 9(10), 3348. https://doi.org/10.3390/jcm9103348 Macfarlane, G. J., Kronisch, C., Dean, L. E., Atzeni, F., Häuser, W., Fluß, E., et al. (2017). Serrat, M., Coll-Omaña, M., Albajes, K., Solé, S., Almirall, M., Luciano, J. V., et al. (2021). EULAR revised recommendations for the management of fibromyalgia. Annals of the Efficacy of the FIBROWALK multicomponent program moved to a virtual setting for Rheumatic Diseases, 76(2), 318–328. https://doi.org/10.1136/annrheumdis-2016- patients with fibromyalgia during the COVID-19 pandemic: A proof-of-Concept RCT 209724 performed alongside the state of alarm in Spain. International Journal of Malfliet, A., Van Oosterwijck, J., Meeus, M., Cagnie, B., Danneels, L., Dolphens, M., Environmental Research and Public Health, 18(19), Article 10300. https://doi.org/ Buyl, R., & Nijs, J. (2017). Kinesiophobia and maladaptive coping strategies prevent 10.3390/ijerph181910300 improvements in pain catastrophizing following pain neuroscience education in Serrat, M., Sanabria-Mazo, J. P., Almirall, M., Musté, M., Feliu-Soler, A., Méndez- fibromyalgia/chronic fatigue syndrome: An explorative study. Physiotherapy: Theory Ulrich, J. L., et al. (2021). Effectiveness of a multicomponent treatment based on and Practice, 33(8), 653–660. https://doi.org/10.1080/09593985.2017.1331481 pain neuroscience education, therapeutic exercise, cognitive behavioral therapy, and McCracken, L. M. (2020). Necessary components of psychological treatment for chronic mindfulness in patients with fibromyalgia (FIBROWALK study): A randomized pain: More packages for groups or process-based therapy for individuals? European controlled trial. Physical Therapy, 101(12), pzab200. https://doi.org/10.1093/ptj/ Journal of Pain, 24(6), 1001–1002. https://doi.org/10.1002/ejp.1568 pzab200 McCracken, L. M., & Keogh, E. (2009). Acceptance, mindfulness, and values-based action Serrat, M., Sanabria-Mazo, J. P., García-Troiteiro, E., Fontcuberta, A., Mateo-Canedo, C., may counteract fear and avoidance of emotions in chronic pain: An analysis of Almirall, M., et al. (2020). Efficacy of a multicomponent intervention for anxiety sensitivity. The Journal of Pain, 10(4), 408–415. https://doi.org/10.1016/j. fibromyalgia based on pain neuroscience education, exercise therapy, psychological jpain.2008.09.015 support, and nature exposure (NAT-FM): Study protocol of a randomized controlled Mease, P., Arnold, L. M., Choy, E. H., Clauw, D. J., Crofford, L. J., Glass, J. M., et al., trial. International Journal of Environmental Research and Public Health, 17(2), 634. OMERACT Fibromyalgia Working Group. (2009). Fibromyalgia syndrome module at https://doi.org/10.3390/ijerph17020634 OMERACT 9: Domain construct. Journal of Rheumatology, 36(10), 2318–2329. Siddall, B., Ram, A., Jones, M. D., Booth, J., Perriman, D., & Summers, S. J. (2022). Short- https://doi.org/10.3899/jrheum.090367 term impact of combining pain neuroscience education with exercise for chronic Merlo, E. M. (2019). Opinion Article: The role of psychological features in chronic musculoskeletal pain: A systematic review and meta-analysis. Pain, 163(1), e20–e30. diseases, advancements and perspectives. Mediterranean Journal of Clinical https://doi.org/10.1097/j.pain.0000000000002308 Psychology, 7(3). https://doi.org/10.6092/2282-1619/2019.7.2341 Sosa-Reina, M. D., Nunez-Nagy, S., Gallego-Izquierdo, T., Pecos-Martín, D., Miller, R. P., Kori, S. H., & Todd, D. D. (1991). The Tampa scale: A measure of Monserrat, J., & Álvarez-Mon, M. (2017). Effectiveness of therapeutic exercise in kinisophobia. The Clinical Journal of Pain, 7(1), 51. https://journals.lww.com/clini fibromyalgia syndrome: A systematic review and meta-analysis of randomized calpain/Citation/1991/03000/The_Tampa_Scale__a_Measure_of_Kinisophobia.53. clinical trials. BioMed Research International. , Article 2356346. https://doi.org/ aspx. 10.1155/2017/2356346 Moher, D., Hopewell, S., Schulz, K. F., Montori, V., Gøtzsche, P. C., Devereaux, P. J., et al. Spijkerman, M. P., Pots, W. T., & Bohlmeijer, E. T. (2016). Effectiveness of online (2012). CONSORT 2010 explanation and elaboration: Updated guidelines for mindfulness-based interventions in improving mental health: A review and meta- reporting parallel group randomised trials. International Journal of Surgery, 10(1), analysis of randomised controlled trials. Clinical Psychology Review, 45, 102–114. 28–55. https://doi.org/10.1016/j.ijsu.2011.10.001 https://doi.org/10.1016/j.cpr.2016.03.009 Moman, R. N., Dvorkin, J., Pollard, E. M., Wanderman, R., Murad, M. H., Warner, D. O., Stegenga, B. T., Nazareth, I., Torres-González, F., Xavier, M., Svab, I., Geerlings, M. I., et al. (2019). A systematic review and meta-analysis of unguided electronic and et al. (2012). Depression, anxiety and physical function: Exploring the strength of mobile health technologies for chronic pain-is it time to start prescribing electronic causality. Journal of Epidemiology & Community Health, 66(7), e25. https://doi.org/ health applications? Pain medicine (Malden, Mass, 20(11), 2238–2255. https://doi. 10.1136/jech.2010.128371 org/10.1093/pm/pnz164 Talaei-Khoei, M., Fischerauer, S. F., Jha, R., Ring, D., Chen, N., & Vranceanu, A. M. Morris, S. B. (2008). Estimating effect sizes from pretest-posttest-control group designs. (2018). Bidirectional mediation of depression and pain intensity on their Organizational Research Methods, 11(2), 364–386. https://doi.org/10.1177/ associations with upper extremity physical function. Journal of Behavioral Medicine, 1094428106291059 41(3), 309–317. https://doi.org/10.1007/s10865-017-9891-6 Moseley, L. (2003). Unraveling the barriers to reconceptualization of the problem in Thieme, K., Mathys, M., & Turk, D. C. (2017). Evidenced-based guidelines on the chronic pain: The actual and perceived ability of patients and health professionals to treatment of fibromyalgia patients: Are they consistent and if not, why not? Have understand the neurophysiology. The Journal of Pain, 4(4), 184–189. https://doi. effective psychological treatments been overlooked? The Journal of Pain, 18(7), org/10.1016/s1526-5900(03)00488-7 747–756. https://doi.org/10.1016/j.jpain.2016.12.006 Moseley, G. L., & Butler, D. S. (2015). Fifteen years of explaining pain: The past, present, Turner, J. A., Anderson, M. L., Balderson, B. H., Cook, A. J., Sherman, K. J., & and future. The Journal of Pain, 16(9), 807–813. https://doi.org/10.1016/j. Cherkin, D. C. (2016). Mindfulness-based stress reduction and cognitive behavioral jpain.2015.05.005 therapy for chronic low back pain: Similar effects on mindfulness, catastrophizing, Moseley, G. L., & Butler, D. S. (2017). Explain pain supercharged. NOI. https://www.pain self-efficacy, and acceptance in a randomized controlled trial. Pain, 157(11), supportjersey.com/media/1084/explain-pain-supercharged-advert.pdf. 2434–2444. https://doi.org/10.1097/j.pain.0000000000000635 Musekamp, G., Gerlich, C., Ehlebracht-Kï Nig, I., Dorn, M., Hï Fter, A., Tomiak, C., et al. Van Breukelen, G. J. (2006). ANCOVA versus change from baseline: More power in (2019). Evaluation of a self-management patient education programme for randomized studies, more bias in nonrandomized studies [corrected]. Journal of fibromyalgia-results of a cluster-RCT in inpatient rehabilitation. Health Education Clinical Epidemiology, 59(9), 920–925. https://doi.org/10.1016/j. Research, 34(2), 209–222. https://doi.org/10.1093/her/cyy055 jclinepi.2006.02.007 Navarrete, J., García-Salvador, M.Á., Cebolla, A., & Baños, R. (2022). Impact of Vlaeyen, J., Crombez, G., & Linton, S. J. (2016). The fear-avoidance model of pain. Pain, mindfulness training on Spanish police officers’ mental and emotional health: A non- 157(8), 1588–1589. https://doi.org/10.1097/j.pain.0000000000000574 randomized pilot study. Mindfulness, 13(3), 695–711. Ware, J. E., Jr., & Sherbourne, C. D. (1992). The MOS 36-item short-form health survey Okifuji, A., & Hare, B. D. (2010). Management of musculoskeletal pain. In M. H. Ebert, & (SF-36). I. Conceptual framework and item selection. Medical Care, 30(6), 473–483. R. D. Kerns (Eds.), Behav psychopharmacol pain manag, 286. Cambridge University PMID: 1593914. Press. Watson, J. A., Ryan, C. G., Cooper, L., Ellington, D., Whittle, R., Lavender, M., et al. Pardos-Gascón, E. M., Narambuena, L., Leal-Costa, C., & van-der Hofstadt-Román, C. J. (2019). Pain neuroscience education for adults with chronic musculoskeletal pain: A (2021). Differential efficacy between cognitive-behavioral therapy and mindfulness- mixed-methods systematic review and meta-analysis. The Journal of Pain, 20(10), based therapies for chronic pain: Systematic review. International Journal of Clinical 1140. https://doi.org/10.1016/j.jpain.2019.02.011. e1–1140.e22. and Health Psychology : IJCHP, 21(1), Article 100197. https://doi.org/10.1016/j. Wegener, S. T., Castillo, R. C., Haythornthwaite, J., MacKenzie, E. J., Bosse, M. J., & The ijchp.2020.08.001 LEAP Study Group. (2011). Psychological distress mediates the effect of pain on Pérez-Aranda, A., Andrés-Rodríguez, L., Feliu-Soler, A., Núñez, C., Stephan-Otto, C., function. Pain, 152(6), 1349–1357. https://doi.org/10.1016/j.pain.2011.02.020 Pastor-Mira, M. A., et al. (2019). Clustering a large Spanish sample of patients with Williams, D. A., Cary, M. A., Groner, K. H., Chaplin, W., Glazer, L. J., Rodriguez, A. M., fibromyalgia using the fibromyalgia impact questionnaire-revised: Differences in et al. (2002). Improving physical functional status in patients with fibromyalgia: A clinical outcomes, economic costs, inflammatory markers, and gray matter volumes. brief cognitive behavioral intervention. Journal of Rheumatology, 29(6), 1280–1286. Pain, 160(4), 908–921. https://doi.org/10.1097/j.pain.0000000000001468 PMID: 12064847. Pérez-Aranda, A., Feliu-Soler, A., Montero-Marín, J., García-Campayo, J., Andrés- Wilson, S., & Cramp, F. (2018). Combining a psychological intervention with Rodríguez, L., Borràs, X., et al. (2019). A randomized controlled efficacy trial of physiotherapy: A systematic review to determine the effect on physical function and mindfulness-based stress reduction compared with an active control group and usual quality of life for adults with chronic pain. Physical Therapy Reviews, 23(3), 214–226. https://doi.org/10.1080/10833196.2018.1483550 12 M. Serrat et al. Behaviour Research and Therapy 158 (2022) 104188 Wolfe, F., Clauw, D. J., Fitzcharles, M. A., Goldenberg, D. L., Katz, R. S., Mease, P., et al. Wright, A. R., & Gatchel, R. J. (2002). Occupational musculoskeletal pain and disability. (2010). The American College of Rheumatology preliminary diagnostic criteria for In D. C. Turk, & R. J. Gatchel (Eds.), Psychological approaches to pain management: A fibromyalgia and measurement of symptom severity. Arthritis Care & Research, 62(5), practitioner’s handbook (pp. 349–364). Guilford Press. 600–610. https://doi.org/10.1002/acr.20140 Zigmond, A. S., & Snaith, R. P. (1983). The hospital anxiety and depression scale. Acta Psychiatrica Scandinavica, 67(6), 361–370. https://doi.org/10.1111/j.1600- 0447.1983.tb09716 13