Background
The prevalence of fibromyalgia (FM) is approximately 1–3 % in the general population, increases with age, and is more prevalent in women than in men [
1]. In addition to persistent widespread pain and allodynia, patients with FM often experience severe fatigue, sleep disturbances, stiffness, psychological distress and/or cognitive impairment [
2‐
5]. Women with FM have been shown to have impaired physical capacity [
6‐
8] and they are also less physically active compared to healthy controls [
9]. FM is a dominating cause of sick leave among female patients with musculoskeletal disorders and has a great impact on quality of life [
6,
10].
Fatigue is a prominent symptom in patients with FM, which limits their work ability and social life [
11‐
13]. Women with FM have described their fatigue in terms of sleepless nights, physical weakness, social withdrawal, loss of mental energy and overwhelming exhaustion [
13]. Socio-demographic aspects such as female gender, younger age, low working capacity and low level of education have been shown to be associated with higher levels of fatigue in FM [
14].
Fatigue is commonly assessed with a one-dimensional visual analog scale (VAS), which enables comparisons across studies. However, fatigue is a complex symptom that interacts with several other common FM symptoms. It is thus recommended to be assessed in multiple dimensions, such as physical, mental and general fatigue in patients with FM, especially in non-pharmacological studies [
15,
16]. Fatigue has been shown to be associated with increased distress, muscular tenderness, and poor sleep quality [
14,
15,
17,
18]. Higher ratings on the subscales of physical fatigue and reduced activity, which are included in the Multidimensional Fatigue Inventory (MFI-20), have been associated with low working capacity, low level of physical activity and impaired physical capacity in women with FM [
15,
19,
20].
Pain catastrophizing influences the perception of pain and other symptoms in many patients with FM, which complicates the treatment and could influence compliance with exercise [
21]. Catastrophic thinking has also been suggested to have an influence on fatigue in FM and in other chronic conditions. However previous research on this topic is scarce [
22].
The most beneficial treatment for FM requires a multidisciplinary approach combining education, pharmacological treatment, exercise and cognitive behavioral therapy [
23,
24]. Exercise has been found to improve feelings of energy and fatigue in various medical conditions [
25]. Different types of exercise are being used for treatment in FM and chronic widespread pain (CWP) in health care, such as aerobic exercise, resistance training, flexibility exercise and body awareness therapy [
26].
Few exercise studies have included measures of fatigue in patients with FM. However the findings of these studies indicate that exercise could decrease fatigue levels [
26‐
29]. Aerobic exercise has been shown to improve the MFI-20 dimension of reduced motivation in female patients with FM [
30,
31] and global outcome measures of physical capacity and, to some degree, pain and the number of tender points in FM [
26].
Resistance exercise has shown positive effects on limitations in activity, pain, global fatigue, depression and muscle strength in patients with FM. However, the quality of evidence of these effects is poor due to the limited number of studies [
29]. The present study is a sub-study of a randomized controlled trial (RCT) showing that resistance exercise improved muscle strength, overall health, and current pain intensity in women with FM, when compared to an active control group [
32]. The resistance exercise intervention was a person-centered approach, which emphasizes active involvement of the patient in planning the treatment that is suggested to enhance the patient’s ability to manage health problems [
33]. The principles of person-centeredness were used in the previously published RCT. The details of the exercise program were planned together with each patient to support each participant’s ability to manage the exercise and the progression in loads [
32].
As high levels of fatigue have been associated with low levels of physical activity and impaired physical capacity in FM [
15,
19,
20], improvement in physical capacity in patients with FM may result in a reduction in fatigue. To our best knowledge, there is no previous study investigating the effects of resistance exercise on multiple dimensions of fatigue in FM.
The primary aim of the present study was to examine the effects of a person-centered progressive resistance exercise program on multiple dimensions of fatigue in women with FM compared to an active control group, and to investigate predictors of the potential change in fatigue. Second, the effect of resistance exercise on sleep, pain catastrophizing, depression, and anxiety were also explored, as these variables have been shown previously to be associated with fatigue.
Discussion
The present randomized controlled trial investigated the effects of a 15-week person-centered progressive resistance exercise program on multiple dimensions of fatigue in 130 women with FM. Significant improvements were found for change in the MFI-20 subscales for general fatigue, physical fatigue, and mental fatigue in the resistance exercise group in comparison with the active control group. When the analyses were adjusted for baseline differences in sleep efficiency the between-group difference was significant for MFI-20 physical fatigue only. The effect size for MFI-20 physical fatigue was small (0.33) but lies within the expected range according to a recent meta-analysis, which investigated the effects of exercise on fatigue in patients with FM [
55]. The MFI-20 physical subscale reflects fatigue related to “physical ability to do things” and “physical condition”, physical components that are expected to improve with exercise. Although the improvement in physical fatigue was small in effect size, it is valuable for patients describing themselves as physically weak and becoming fatigued after doing very little [
56], which causes deterioration in their quality of life and ability to manage daily activities. The MFI-20 subscale for physical fatigue has been used separately by the Outcome Measures in Rheumatology (OMERACT) group in analyses aiming to identify subgroups in FM [
57].
A previous study found that decreased fatigue in patients with FM engaging in exercise was associated with changes in adipokines and insulin-like growth factor-1, which appear to be biological correlates of exercise and fatigue [
58]. We were also interested in investigating which variables could predict the possible change in fatigue. Participating in resistance exercise combined with working fewer hours per week at baseline predicted greater improvement in the MFI-20 subscale for physical fatigue. The PSQI for sleep efficiency predicted improvement in the MFI-20 for general fatigue, which indicates that the women with FM who had worse sleep efficiency at baseline were more likely to improve their general fatigue regardless of whether they participated in resistance exercise or in the active control group. Sleep efficiency in the PSQI refers to the time asleep per night in relation to the time spent in bed. These findings indicate that women with FM who have the worst sleep efficiency might have the most to gain from any intervention. However, the explained variance ranged from 5 –4 % in the analyses of the MFI-20 subscales, and the improvement in fatigue was reasonably influenced by other factors not investigated in the present study.
Variables that have been previously found to be associated with dimensions of fatigue were included in the correlation analyses; however, only a few variables appeared to be associated with change over time in fatigue. The participants’ age or duration of pain did not appear to have an influence on change in fatigue, nor did their level of psychological distress or physical capacity. These results indicate that women with FM could gain improvements in fatigue by resistance exercise regardless of individual factors. Similar results have also been found for improvements in pain disability [
59].
Fatigue is a symptom with a great negative effect on daily life in women with FM [
11,
13,
60] and has been recommended to be assessed in multiple dimensions [
15,
61], yet the effects of resistance exercise on multidimensional fatigue in FM have not been previously studied. However, a few studies have investigated the effect of resistance exercise on global fatigue assessed with a VAS [
62,
63]. In the present study the FIQ for global fatigue was included for exploratory analysis. There was significant improvement in the FIQ for global fatigue within the resistance exercise group but there were no significant differences in change in the FIQ for global fatigue between the resistance exercise group and the control group. These results are in line with previous studies by Jones et al. [
62] comparing resistance exercise with flexibility exercise, and by Häkkinen et al. [
63] comparing resistance exercise with a control group in FM; both studies showed a significant change within the resistance exercise group in a VAS for global fatigue, but there were no significant differences in the change in global fatigue in comparison with controls. These findings endorse the use of a multidimensional assessment of fatigue in terms of physical fatigue, which was sensitive to change induced by resistance exercise.
Exploratory analyses were carried out in the present study aiming at investigating the effects of resistance exercise on the PSQI, the PCS and the HADS as compared to the active control group. In the analyses of change over time in the PSQI, the resistance exercise group had significant within-group improvements in the subscale for sleep quality and the active control group reported significant improvement in the subscale for needing medications to sleep, after the 15-week intervention. However, there were no significant between-group differences in change for any of the PSQI subscales. This is line with the results of a previous study of resistance exercise in women with FM [
63].
There were significant within-group improvements over time in pain catastrophizing in the PCS total score and all three subscales in the resistance exercise group. However, there were no significant between-group differences in change, possibly because the control group also tended towards improvement in the PCS.
No significant changes were found for change in depression or anxiety assessed with the HADS in the resistance exercise group or the active control group. Also in previous exercise studies, the effect on depression and anxiety in FM has been found to be limited [
31,
64].
Recent publications have recommended resistance exercise for patients with FM [
65,
66]. The resistance exercise program in the present study had a person-centered approach and was progressively increased over 15 weeks. Over 60 % of the participants managed to increase the loads up to 80 % of 1 RM and the attendance was satisfactory at 71 %. Only 5 (7 %) of the participants in the resistance exercise group discontinued the intervention due to increased pain, which indicates that a majority of women with FM tolerate individually tailored resistance exercise twice a week for over 3 months. The resistance exercise program had a person-centered approach, which most likely contributed to the high attendance rate and low occurrence of adverse effects, as the approach enhances self-efficacy and sense of control in the participants. The resistance exercise program in the present study had similarities with the programs in the studies by Jones et al. [
62] and Häkkinen et al. [
63], which also were progressed and performed twice a week [
62]. Relaxation therapy was chosen as the active control treatment in the present study and was assumed to improve overall wellbeing in the women with FM.
Limitations
The present study is a sub-study and the statistical power was calculated with regards to the primary analysis published previously [
32]. The number of included participants was also considered to be sufficient for the aim of the present study, and there was a significant difference between the groups in change in physical fatigue. The results of the present study must be interpreted with caution because the upper limit of the expected number of false significant results was calculated to be 0.21 for the primary outcomes, which indicates that 0–1 of the significant results could be false. A large number of tests of correlation were also performed in the analyses of predictors, and the values of explained variance (
R
2) in the multiple linear regression analyses were low, ranging from 0.05 to 0.14, which could be in the margin of error for the subscales.
Positive expectations of exercise have been found to play a role in the effect of exercise on psychological outcomes [
67]. The participants in the present study were recruited by newspaper advertisement, which could have attracted persons with FM with expectations of improvement and a positive attitude towards resistance exercise. This might have influenced the magnitude of improvement and compliance with the exercise protocol. However, the same recruitment method was used for both groups and they were recruited simultaneously, thus the recruitment method would not have affected the outcome in group comparisons.
Abbreviations
ACR, American College of Rheumatology; CWP, chronic widespread pain; FIQ, Fibromyalgia Impact Questionnaire; FM, fibromyalgia; HADS, Hospital Anxiety and Depression Scale; LTPAI, Leisure Time Physical Activity Instrument; MFI-20, Multidimensional Fatigue Inventory; PCS, Pain Catastrophizing Scale; PSQI, Pittsburgh Sleep Quality Index; RCT, randomized controlled trial; RM, repetition maximum; VAS, visual analog scale
Acknowledgements
We would like to thank all colleagues who performed examinations and supervised the groups in Gothenburg, Alingsås, Linköping, and Stockholm. The study was supported by the Swedish Rheumatism Association, the Swedish Research Council, the Health and Medical Care Executive Board of Västra Götaland Region, ALF-LUA at Sahlgrenska University Hospital, Stockholm and Östergötland County Councils (ALF), and AFA Insurance and Gothenburg Center for Person Centered Care (GPCC). The authors declare no conflicts of interest.