|Home | About | Journals | Submit | Contact Us | Français|
Due to the dynamic and complex nature of chronic pain, successful treatment usually requires addressing behavioral, cognitive and affective processes. Many adjunctive interventions have been implemented in fibromyalgia (FM) treatment, but few are supported by controlled trials. Herein, some of the more commonly used nonpharmacologic interventions for FM will be described and the evidence for efficacy presented. Clinical observations and suggestions will also be offered including using the principles outlined in the acronym “ExPRESS” to organize a comprehensive, nonpharmacologic pain management approach.
Treating patients with chronic pain conditions has long held challenges and been rife with pitfalls for healthcare professionals. Pain is a complex and dynamic phenomenon influenced by genetic, physiological, cognitive, affective, behavioral and social factors. Melzack and Wall’s gate-control theory revolutionized the understanding of and treatment for chronic pain . Central to this theory is the existence of a gating system at the dorsal horn of the spinal cord that can control pain transmission from the periphery to the somatosensory cortices in the brain. The gating of pain signals is thought to be controlled by both peripheral input and the neural centers that govern thoughts, emotions and behaviors . Gate-control theory explains why certain factors such as depression and anxiety worsen the experience of pain, while other factors like active coping, positive affect, and social support moderate the experience of pain .
Factors resulting from living with chronic pain (e.g., poor sleep, reduced physical activity, social withdrawal) are the very same factors that put one at risk for even greater physical pain. Patients with fibromyalgia (FM) bear the additional burden of battling long-held misconceptions that FM is a psychiatric illness. As with most chronic pain conditions, co-morbid mood and anxiety disorders commonly occur in FM (29% and 27% , respectively). Further, a lifetime diagnosis of a major mood disorder has been observed in as many as 74% of FM patients . Thus psychiatric co-morbidity and a lack of objective evidence of disease have led to the belief that FM is a somatization disorder – psychiatric in nature and a “fashionable” expression of psychological distress . In the past decade, however, innovative research inspired by advances in the neuroscience of pain has greatly contributed to the understanding of the pathophysiology of FM. For example, altered pain processing in FM has been demonstrated in functional magnetic resonance imaging studies (6–7), while others have identified a deficiency in an important central analgesic system resulting in diminished diffuse noxious inhibitory control (DNIC)(8). This knowledge has resulted in new ways of conceptualizing FM and its treatment.
Medications that target modifying pain centrally have shown some efficacy and been approved by the FDA specifically for the treatment of FM pain. However, like most rheumatologic conditions, FM is symptomatically heterogeneous thus rendering a single pharmacologic approach for all patients inadequate. FM patients vary significantly in the type and severity of symptoms experienced, the presence of medical and psychiatric comorbidities, and a range of human factors (e.g., genetic, cognitive, behavioral, social); each factor influences the experience of pain and treatment outcomes. It is because of the complexity of pain and heterogeneity of FM patients that treating FM using a multidisciplinary approach [9–12] and considering the particular needs of patient subgroups [13–15] are frequently recommended.
A multidisciplinary approach has been found to provide superior outcomes when compared to monotherapy . At the heart of this approach is taking into account the unique characteristics of each patient and adding adjunctive nonpharmacologic interventions to evidence-based use of medication. The importance of including exercise in the treatment of FM has been substantiated in a number of studies reviewed by Jones (this volume). In addition to exercise, patient education, cognitive-behavioral therapy, relaxation, biofeedback, and other complementary and alternative medicine (CAM) approaches are gaining empirical support and should be considered. Herein, we briefly present an overview of these techniques and the evidence for their inclusion as fundamental elements of FM treatment.
Most experts agree that an educational or psychoeducational treatment component is useful if not necessary when treating FM . Such educational programs target increasing understanding of the complex nature of the interactions between neurobiological processes, behaviors such as sleep and/or activity levels, and symptoms. These programs have varied foci, but usually try to allay the stigma often attached to FM and similar disorders. Goldenberg  has recently set out recommendations regarding education that seem well founded. He points out that: “When educating patients, a core set of information should be provided that includes a detailed discussion of potential pathophysiological mechanisms in the context of the biopsychological model. The clinician must dispel the notion that the absence of organic disease means that the symptoms are psychogenic” (p. 31). Some clinicians have expressed concern that the labeling of FM in itself might worsen symptoms. However, the one prospective study on this topic found that the diagnosis had no adverse effects, and may have actually improved function over 18 months . Thus careful education seems warranted.
Yet, only limited data are available to support this contention. Beyond a number of studies that failed to find superiority for other interventions when compared to an educational control group [18–19], only two well controlled trials have been reported. Burckhardt and colleagues assigned FM patients to an education only condition, an education plus physical training condition, or a delayed treatment waitlist control . Both active treatment groups improved on subjective ratings and reports of physical activity compared to controls. Burckhardt has published a review and treatment guide to the self-management of FM . More recently, Rooks et al.  completed a randomized controlled trial with 207 confirmed FM patients who were assigned to one of four groups: (1) an aerobic and flexibility exercise group; (2) a strength training, aerobic, and flexibility exercise group; (3) the Fibromyalgia Self-Help Course (FSHC); or (4) a combination of the above. The primary outcome was change in physical function from baseline to completion of the intervention. Secondary outcomes included social and emotional function, symptoms, and self-efficacy. The combination group showed the greatest improvement. The Education or self-management group did improve, but significantly less than the groups that included physical training. While more research is clearly needed, it appears that education will be most effective in multi-modal interventions.
CBT combines interventions from both cognitive and behavior therapies. Cognitive therapy is based on the premise that modifying maladaptive thoughts results in changes in both affect and behavior . Therefore, errors in thinking such as overgeneralizing, magnifying negatives, minimizing positives and catastrophizing are challenged and replaced with more realistic and effective thoughts, thus decreasing emotional distress and self-defeating behavior. More specific to FM, catastrophizing, or the belief that the worst possible outcome will occur, has been associated with pain severity [24–26], decreased functioning  and affective distress in FM [25–26]. In cognitive therapy, catastrophic thoughts like “My pain is awful and there is nothing I can do about it” are reframed to “As bad as my pain might get there are things I can do to make it at least a little better.”
In contrast to cognitive therapy, behavior therapy is rooted in the theory that inner states (thoughts and feelings) are less important than the use of operant behavior change techniques to increase adaptive behavior through positive and negative reinforcement and extinguish maladaptive behavior by using punishment. In FM, a number of behavioral techniques are applicable including behavioral activation (getting patients moving again), graded exercise (initiating exercise, then slowly increasing activities), activity pacing (not over doing it on days patients feel good and remaining active on days they feel bad), reducing pain behaviors (not reinforcing behaviors associated with secondary gain), sleep hygiene (identifying then changing behaviors know to disrupt sleep), and learning relaxation techniques to lower stress (e.g., breathing, imagery, progressive muscle relaxation).
Meta-analyses have shown that CBT has significant empirical support for its effectiveness in treating psychiatric illnesses like depression  and anxiety disorders [27–28], which are common in FM. Thus, addressing psychiatric comorbidity alone provides a good rationale for adding CBT to usual medical treatment for a subgroup of FM patients ; however, CBT has also proven to be helpful for a number of medical conditions including chronic pain . A review of the CBT literature related to FM indicates that a multitude of interventions have been described to be “CBT” - some perhaps inappropriately so. All CBT interventions are not equal with many including only modest elements of cognitive therapy and instead relying heavily on behavioral interventions.
Given the limitation that CBT is not a single discrete intervention akin to a single drug given at a particular dose, there is evidence suggesting that CBT may be an effective adjunctive treatment for some patients with FM. Two initial open pilot studies reported improvements in pain intensity  and the ability to control pain , as well as less emotional distress in FM patients . A larger study with a waitlist control (FM=79, Waitlist=49) reported improvements in pain, functioning and emotional distress . Then, two more studies using educational control groups found positive effects for CBT, but none of the effects were significantly greater than those of the control groups [34–35].
Two more recent studies have yielded promising results. Williams and colleagues  randomly assigned 145 patients with FM to either 4 weeks of group CBT (6 sessions) or standard medical care. Twenty-five percent of patients with FM receiving CBT met criteria for being a “treatment responder” (i.e., sustained improvement in functional status), compared to 12% of those receiving only standard medical care. Pain scores did not change significantly for either group, but patients considered “treatment failures” in the CBT group showed no worsening of symptoms or functional status unlike the waitlist controls who demonstrated deterioration in energy and physical role functioning. The authors surmised that while only a subgroup of patients responded to CBT, there could be buffering effects for many more patients.
In the most compelling study to date, Thieme et al. randomly assigned 125 patients with FM to either CBT (n=42), operant behavior therapy (OBT; n=43) or an attention control group (n=40) . OBT consisted of behavioral interventions to reduce pain behaviors, while CBT addressed modifying maladaptive thoughts, problem solving, decreasing psychological stress, pain coping strategies and relaxation. They found that when compared to the attention control, both CBT and OBT resulted in greater improvement in pain, decreased emotional distress and improved physical functioning for up to one year post-treatment . Patients in both treatment groups also had fewer physician visits when compared to those in the control group. Further, the effect sizes for improvement were large for both CBT and OBT, but for the most part the differences between both active treatments were not significant. They did observe that patients in the CBT group demonstrated sustained increases in coping and decreases in catastrophizing likely contributing to persistent improvements in emotional distress. In fact, patients in the attention control group which consisted of unstructured group discussion about FM showed increases in catastrophizing and pain intensity 6 months post-treatment.
Effective CBT interventions for FM will likely target the modification of maladaptive thoughts and expectations, thus improving mood, perceived stress, pain coping and problem solving, while including behavioral interventions that specifically address ameliorating FM symptoms (e.g., sleep hygiene, relaxation training, activity pacing). In FM, the primary goal of CBT treatment is to increase self-management which includes moving patients toward more adaptive beliefs regarding their ability to cope with and control pain and other symptoms, as well as taking action to decrease FM symptoms and stress resulting in increased functioning. Because the evidence for adding CBT to pharmacological treatment for FM remains modest, more randomized controlled trials are needed. Further, only subgroups of FM patients may be likely to respond to CBT such as those with greater emotional distress, fewer coping skills and/or less social support  or those who believe the treatment will be effective at the outset . Future studies of CBT in FM should carefully explore individual factors associated with response to CBT, as well as what specific elements of CBT are most highly associated with a positive response to treatment.
There is substantial overlap between CBT and behavioral interventions. Most CBT includes one or more forms of behavioral relaxation; although, some of these techniques have evidence for efficacy in the absence of a cognitive therapy component. Relaxation techniques likely to be helpful for FM symptoms include, but are not limited to, progressive muscle relaxation, autogenic training, guided imagery and meditation. Biofeedback can also be subsumed under this umbrella but possessing multiple types and having been the recipient of more empirical attention, biofeedback will be described at greater length in the following section.
Because psychological distress and dysfunction of the stress response systems have been observed in subgroups of FM patients , stress management has been a target of treatment. Progressive muscle relaxation (PRM)  and autogenic training typically serve as the substrate of behavioral intervention for chronic pain [42–43]. This is true for FM even though no randomized controlled trials have evaluated PRM in isolation and two trials of autogenic training failed to find superiority for it when compared to other treatment conditions [44–45]. Despite the lack of direct evidence, clinical experience and the knowledge that both relaxation techniques are commonly part of CBT for FM [36,46], their efficacy is generally accepted.
PRM involves the systematic tightening and relaxing of various muscle groups with the goal of decreasing muscle tension overall and thus ameliorating anxiety which was presumed to be linked to muscle tension . In FM, PMR has the added benefit of emphasizing to the patient the difference between muscles that are tense and those that are relaxed since many patients persistently tense their muscles unknowingly which can contribute to their pain. One caveat, FM patients should be cautioned to not tense muscles too tightly during this exercise since this could result in exacerbating pain. In contrast, autogenic training involves repeating phrases such as, “My arms are heavy and warm” and visualizing heaviness and warmth in the arms . The exercise invokes images associated with a relaxed state while moving the focus from one body area to the next. Verifiable warming in the extremities is typically experienced , which can be helpful for FM patients who frequently report cold intolerance and Raynaud’s-like symptoms . Some evidence for including both PMR and autogenic training comes from a study by Allen and colleagues that included FM patients amongst others with similar symptoms . Allen et al. reported that a manualized CBT protocol that included PMR and autogenic training as central aspects of treatment resulted in decreased symptom severity when compared to augmented medical care .
Autogenic training includes elements of guided imagery, but guided imagery alone involving engaging all senses in experiencing pleasant places or circumstances has proven to be helpful for some with FM. Guided imagery enhances muscle relaxation and can serve as a powerful distraction from pain. In a randomized controlled trial of 55 women with FM it was found that those in the guided imagery arm (n=17) had less pain compared to the control group . In another study comparing a 6-week guided imagery intervention to treatment as usual, patients with FM receiving guided imagery demonstrated improved functional status and reported a greater sense of self-efficacy for managing pain although actual pain reports did not change . A recent pilot study reported positive findings for the use of guided imagery specifically for Hispanic FM patients noting significant improvements in symptoms, functioning and self-efficacy for managing pain . Lastly, in a small open study of female juvenile FM patients, a combination of PMR and guided imagery was found to reduce pain and improve sleep in the majority of patients  illustrating the potential benefit of using these interventions in combination.
Meditation-based stress reduction can also take a number of forms although “mindfulness” meditation is frequently used as an intervention for medical populations. In mindfulness meditation, the patient is directed to focus on one thing, an “anchor,” be it a sound, visualizing a pleasant scene or their breathing. Thoughts are to remain present oriented and analytical musings are to be avoided in favor of focusing on the meditation anchor. A few studies have examined the efficacy of meditation-based interventions in FM. In an early study of 77 FM patients enrolled in a meditation-based stress reduction program, the authors reported that the scores of all of the patients completing the program improved and 51% of completers had moderate to marked improvement . More recently, a randomized controlled trial comparing women with FM assigned to an 8-week mindfulness meditation program (n=51) to those in a waitlist control group (n=40) found that depressive symptoms improved significantly in the meditation group . Taken together there is some, albeit inconclusive, evidence that relaxation techniques can be effective adjunctive treatment for FM. Here too, randomized controlled trials using attention, educational and active comparators are needed.
As has been discussed, it is becoming increasingly evident that FM is a complex systemic disorder with at least some central mediation of symptoms. An additional perspective has emerged that implicates the autonomic nervous system as pivotal to at least some subgroups of FM patients [56–61]. Martinez-Lavin has championed this approach and with others, has produced a substantial body of data. There is reasonably good evidence that autonomic nervous system functioning in some FM patients can be characterized by elevated sympathetic tone, by poor parasympathetic tone, and by an abnormal 24-hour autonomic cycle [56–61].
Based on this orientation, heart rate variability (HRV) biofeedback has emerged as a potential useful treatment for FM. Pioneered by Lehrer, Vashillo, and Gevirtz, [62–65] this approach utilizes the discoveries made through the centuries by Yoga Swami’s and other eastern disciplines utilizing slow breathing techniques coupled with mindful mental states or mantras (see section above on meditation). Sensors detect beat-to-beat heart rate, HRV parameters, respiration wave forms, and finger temperature. This “feedback” is displayed on a computer monitor situated in front of the seated patient. Patients learn to produce a characteristic heart rate pattern (respiratory sinus arrhythmia) by breathing at a certain rate (e.g., six breaths per minute), that over time becomes a very smooth exaggerated sine wave. HRV biofeedback has produced good results for asthma , chronic obstructive pulmonary disease , cardiac rehabilitation , irritable bowel syndrome , and hypertension . Three studies to date have attempted to use HRV biofeedback in the treatment of FM [71–73]. In a small pilot study, Hassett et al. treated 12 women over 10 sessions and found the HRV biofeedback group to improve in most FM symptom areas (sleep, pain, fatigue, depression, and overall functioning) . Importantly, physiological functions such as heart rate variability, and blood pressure variability improved over time as well. In a small controlled study with chronic fatigue patients, Stevens and Gevirtz compared HRV biofeedback combined with sleep hygiene and activity management to a waitlist control . The active treatment group showed improvements in fatigue and depression, while the controls either declined or remained constant on these symptoms. Recently, Hassett and colleagues have completed a randomized controlled trial comparing HRV biofeedback to a relaxation condition. Although the data have not yet been fully analyzed, preliminary analysis of the first 68 patients indicated that compared to the control, the patients in the HRV group experienced an increase in functioning from baseline to the final session . While much more research is needed, HRV biofeedback training may offer promise since it targets a known physiological component of FM and is therefore seen by the patient as a very acceptable treatment in our collective experience.
Several studies exist using other biofeedback approaches. Buckelew and colleagues conducted a randomized controlled trial comparing electromyogram (EMG) biofeedback (n = 29), exercise training (n = 30), combination treatment (biofeedback and exercise) (n = 30) and an educational/attention control (n = 30) . Compared to the control, they found patients in the treatment groups showed improvements in self-efficacy for functioning and better tender point index scores. The treatment groups reflected equivalent benefit, while there was a slight deterioration within the control. More recently, an Indian study used surface EMG biofeedback (n = 15) compared to a sham feedback condition (n = 15) with FM patients and found the active biofeedback to reduce tender points and subjective symptoms and result in improvements on functioning and the six-minute walk test . In addition, several small open trials conducted in Europe found that FM patients receiving EMG biofeedback reported improvement in pain [76–77], sleep disturbance , headache  and experienced persistent clinical benefit . However, there is one controlled trial where patients assigned to either a fitness program (n=58) or surface EMG biofeedback enhanced progressive relaxation protocol (n=56) failed to show significant improvement compared to controls (n=29) . One caveat, the lack of effectiveness for the fitness program is not consistent with most other findings, raising questions about this particular sample. Despite this contrary result and the fact that in many cases it is difficult to analyze the methods used, the generally positive findings across controlled trials and small pilot studies suggest that EMG biofeedback may be a promising treatment for at least some patients with FM. Lastly, a small case study on three patients  used neurofeedback (EEG biofeedback) over 10 sessions and found that all patients reported decreased symptoms. Again, encouraging findings beg for more rigorous follow-up studies.
FM patients overwhelmingly have sought CAM interventions . Yet, as is the case for so many disorders, very little scientific evidence exists for the efficacy of such approaches. Furthermore, deciding what treatments fall into this category is a perilous endeavor; however, a few treatments have been investigated.
Massage is a widely used CAM therapy for patients with FM, and based on patient survey data, the intervention with the highest satisfaction levels . Only one study using a comparison or control was located . Brattberg compared connective tissue massage (n=23) to a no treatment control (n=25) over 15 treatments . Pain, depression, use of analgesics and quality of life were improved in the treatment group compared to the controls. Yet, the treatment effects dissipated over a 6-month follow-up period.
Like massage therapy, chiropractic treatments have become a very popular modality for FM patients . Despite its popularity, few randomized controlled trials have been done with FM patients using chiropractic modalities. In a recent review , the authors concluded “…Lastly, other CAM therapies have neither well-designed studies nor positive results and are not currently recommended for FMS treatment (chiropractic care)” p. 667.
The term “Qigong” generally describes a number of traditional Chinese therapies and exercises all believed to facilitate the flow of vital energy or “chi” . Astin and colleagues  conducted a randomized controlled trial where they assigned 128 FM patients to either an 8-week intervention that included a mind-body training group (mindfulness meditation and Qigong movement therapy) or an educational support group. Both groups registered statistically significant improvements across time for the Fibromyalgia Impact Questionnaire, Total Myalgic Score, pain, and depression. However, there was no difference in either the rate or magnitude of these changes between the mind-body training group and the education control group. Both groups maintained gains at the 6-month follow-up. Mannerkorpi et al. conducted a similar controlled trial of Qigong movement therapy with similar results . It has been noted that both studies were hindered by the lack of qigong practice which is supposed to take place daily and with high intensity in order to generate sufficient qi flow .
In a study using Qigong as a manual therapy , 10 women with FM received external Qigong therapy provided by a Chinese Master over a 3-week period. Patients were then assessed post-treatment and at 3 months. Improvements (with large effect sizes) were observed in pain, functioning, depression and self–efficacy. No control was used for this pilot, but the magnitude of the symptom reductions warrant further investigation. Lastly, one uncontrolled pilot study  evaluated the effect of 6 weeks, bi-weekly T’ai Chi sessions for 39 women with FM. Though there was a high drop-out rate, the group significantly reduced symptoms and increased quality of life. These techniques offer some promise of efficacy, but all need more rigorous assessment to be considered in an evidence-based treatment mix.
Mayhew and Ernst recently reviewed the evidence concerning acupuncture and FM. They were able to find 5 studies that could be reviewed . They rated their quality as variable, but independent of quality, they found mixed results. They asserted that none of the trials included adequate placebo conditions weakening their scientific value and concluded that acupuncture treatment was not supported by rigorous clinical trials and thus could not be recommended for FM. Since this review, one randomized controlled trial was published. In it, 34 women with FM receiving acupuncture plus tricyclic antidepressants and exercise were compared to 24 women receiving tricyclic antidepressants and exercise only (controls) . After 20 sessions of treatment Targino et al. observed that the women in the acupuncture condition reported significantly decreased levels of pain and improved quality of life compared to the controls. The positive effects persisted for 3 months then dissipated over the 2-year follow-up period. Finally, in a randomized trial of acupuncture for 114 patients with FM evaluating methodology related to acupuncture – correct needle placement and needle stimulation which are presumed to both be necessary to maximize effects . Harris and colleagues reported that although 25–35% of patients had significant decreases in pain, correct needle placement and needle stimulation were not a factor suggesting the possibility for a strong placebo response .
Several well-controlled studies do exist that evaluated spa type bath therapies that have been used for centuries to ease pain. A recent review  found 10 studies of sufficient quality for review. Mean methodological quality was 4.5/9 on the van Tulder scale. Positive outcomes were reported for pain, health-status and tender point count. There is strong evidence for the use of hydrotherapy in the management of FM. However, most studies were short term and few used credible placebo conditions. It does seem, however, that the conventional wisdom that warm water baths relieve pain in the short term is well founded.
Many other CAM modalities have been studied, especially various botanicals . Sarac and Gur  have recently reviewed evidence for herbal and nutritional supplements such as St. John’s Wort, Genseng, Valeria, botanical oil, melatonin, magnesium, DHEAS, NADH, SAM-E, growth hormone, chlorella pyrenoidosa, 5-HTP, and a number of dietary supplements. Many of these have shown promising results in early trials, but mixed results are increasingly common as the studies become methodologically more sophisticated. Additional work is needed to be able to know which, if any, of the many touted botanicals may be of lasting help for FM.
The research, as well as our clinical experience, indicates that the addition of education and a behavioral or cognitive-behavioral component to FM treatment protocols is warranted. Especially when combined with other modalities such as exercise, sleep hygiene, or activity pacing, using some form of behavioral intervention seems to add to the efficacy of the treatment. An important caveat however applies: It is important to avoid any suggestion that the symptoms are “all in your head” when recommending these treatments. It is easy to forget the stigmatizing aspects of any mental health diagnosis in our society. We have found that using a physiologically based label (like “biofeedback” or “stress management”) greatly reduces the perception of the patient that he or she is being “dumped” to a “shrink”. A recent informal study of ours (RG) at a major military medical center indicated a strong preference for referrals for “biofeedback” vs. CBT. Once the patient understands the nature of the “mind/body” interaction, further suggestions seem to be accepted without resistance.
For daily clinical practice, we suggest using the principles of comprehensive non-pharmacological pain management represented by the acronym ExPRESS. Ex is for Exercise as described by Jones (this volume). P is for Psychiatric comorbidity since both depression and anxiety disorders are common in chronic pain conditions and contribute significantly to pain and disability. R is for Regaining function which in FM often involves helping patients with activity pacing so that they do not do too much one day when they feel good and do too little on days that they feel bad. E is for Education where simply informing a patient where on the Internet they can find reliable information can be a good start. We suggest referring patients to websites hosted by the Arthritis Foundation (http://www.arthritis.org/disease-center.php?disease_id=10) and the National Fibromyalgia Association (http://www.fmaware.org/site/PageServer). S is for Sleep hygiene which is necessary for many who have developed counter-productive habits. Lastly, S is for Stress management which includes any number of elements including CBT, relaxation techniques, hydrotherapy and gentle exercise to name just a few.
Taking a comprehensive, multidisciplinary approach for the treatment of FM can be challenging for most healthcare professionals not practicing in academic settings. Fortunately, there are innovative tools available to assist them in providing care for FM and/or to enhance patients’ self-management skills. One exceptional tool can be found at the website KnowFibro.com. Here, patients can complete a brief online questionnaire to receive an individualized series of self-help modules which might consist of education, activity pacing, sleep hygiene, relaxation and goal setting. Including evidenced-based non-pharmacological treatment can be greatly facilitated by taking advantage of a resource such as this.
In conclusion, although there is some encouraging evidence for several non-pharmacological modalities like CBT, more controlled trials are needed; especially those that consider combinations of treatments. Further, intervention studies in FM should also explore individual factors to identify which patient subgroups would be the most likely to respond to what particular treatment.
This work was supported by Grant No. P20-MH-074634, National Institutes of Health, “MUPS in Primary Care Research Center.”
The authors are grateful for the administrative support of Shantal Savage and to the individuals with fibromyalgia who share with us their compelling stories in clinical practice and enthusiastically volunteer for our studies.
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.