Role of Cognitive Behavioral Therapy in Fibromyalgia: A Systematic Review

A literature search of articles from 2002-2019 was performed using Medline, Embase, Cochrane, LILACS, IBECS, CRD, and Epistemonikos databases, to analyze the effects of Cognitive-Behavioral Therapy (CBT) in the treatment of fibromyalgia. Twenty-seven articles were selected in which CBT was performed exclusively by specialist physicians, associated or not with conventional pharmacological treatment and/or physical exercise. In most articles, CBT worked with self-knowledge and cognitive restructuring, attempting to reduce pain perception, and it showed a general improvement in daily activities by decreasing patient’s limitations, such as morning stiffness. The literature showed significant correlations of CBT in pain processing over time. When CBT was compared to conventional pharmacological therapy, a certain superiority of CBT could be observed concerning the quality of life, catastrophizing, and acceptance of pain. However, when they were simultaneously applied, this improvement in quality of life was not observed.


Introduction
Fibromyalgia (FM) is a common disease, with a prevalence in the general popu-

Eligibility Criteria
Developed based on the acronym PICO, adapting to their respective 4 points: Population: Patients aged 18 years or over and diagnosed with fibromyalgia (according to the recognized diagnostic criteria) were included in the study.
Intervention: Use of cognitive behavioral therapy in fibromyalgia patients alone or associated with other therapies.
Comparison: Fibromyalgia patients undergoing other types of therapy, another type of treatment, of no treatment at all.
Outcome: All possible outcomes of patients after the use of cognitive behavioral therapy in studies.

Inclusion and Exclusion Criteria
Inclusion: Portuguese, Spanish and English languages; studies performed in humans; there was no restriction on the year of publication.
Exclusion: studies that did not address CBT, other pain syndromes or other rheumatologic diseases, secondary studies, theses and dissertations.

Study Resources
The research was carried out in September 2020, updated in April 2021 in the following online databases: Medline, Embase, Cochrane, LILACS, IBECS, CRD and Epistemonikos.

Search Strategy and Data Extraction
The search was performed with the association of terms "Fibromyalgia", "Positive Psychology", "Cognitive Behavioral Therapy", and their respective synonyms, with Boolean operators according to the most appropriate search strategy for each database.
Each study was initially evaluated by its title and abstract by two researchers, using the Rayyan system (rayyan.qcri.org), allowing the evaluator to be blinded to the other's analysis. In case of disagreement, the study was analyzed by a third party.
After the analysis by title and abstract, the articles were fully read, and those that were not in accordance with the inclusion criteria were excluded. From those selected, the following data was extracted: type of study, objective population (number of people, sex and age), study duration, use of pharmacological therapy duration of cognitive behavioral therapy, use of other types of therapy, guidance received by patients, adherence to treatment, analysis of disease progression or regression and outcome. All data obtained were extracted by a researcher and revised by a second researcher, using an excel spreadsheet. Open Journal of Rheumatology and Autoimmune Diseases [11], the quality of the work methodology, and the presence of biases in the included studies were analyzed by two independent reviewers using the HTA

KMET (Standard Quality Assessment Criteria for Evaluating Primary Research
Papers from a Variety of Fields) [12]. The selection of a representative sample of participants, the randomization of patients selected in the participating groups, the blinding of participants and researchers, a similar form of assessment for all groups, presence of incomplete data, selection of presented results, and other biases were evaluated. All studies were evaluated for each type of bias as low risk, high risk and doubtful risk and according to the probability of their bias, the studies as a whole were classified as low, medium or high risk. A study with low risk was one that was rated as having a low probability of bias in all of the biases analyzed. A moderate risk job was one that had 1 or 2 bias ratings as high or doubtful. Papers that had 3 or more assessments of high or doubtful biases were classified as high risk.

Identification and Selection of Studies
A total of 1364 studies was analyzed. After excluding 296 duplicates and analyzing the title and abstract, a total of 110 articles were selected for full reading, of which 27 were included in the review. The distribution of articles can be seen in Of the 2273 patients with fibromyalgia or strongly suspected of having fibromyalgia, according to primary studies, the majority were women, aged 18 years and over. In most studies, the average age was between 40 and 50 years old.

CBT and Fibromyalgia
Cognitive Behavioral Therapy was carried out exclusively through sessions with therapist psychologists, accompanied or not by specialist physicians, over specific periods. Some articles have supported therapy with other modalities of therapeutic techniques, such as standard pharmacological treatment and hypnosis [18].
In most articles, CBT sought to work on self-monitoring, self-knowledge, and cognitive restructuring exercises to reduce the intensity and regress the main FM symptoms [16].
Overall, 78.57% of the studies observed regression of at least one FM symptom, whether physical (such as pain, stiffness, sleep, and fatigue); or psychological (such as anxiety, stress, and depression). Questionnaires [19], pain scores [21], analysis of variance [36], and subjective clinical impressions [27] were implemented to analyze the improvement in fibromyalgia as the treatment with CBT evolved. The complications of these patients were not scruntinized by the articles analyzed. The articles details can be seen in Table 1.

Evaluation of the Quality of Articles
Of the 27 studies, 3 papers were at low risk [21] [28] [38]. 14 at moderate risk [13] [26] had 126 participants, of which only 57.14% completed the study. Despite the high overall compliance, even with more than half of the patients fully adhering to treatment, it conferred no connection with the success rates [14].  "Life control" improved (20%), as well as "affective suffering" (15%), "Vital exhaustion" (12%), "stress behavior" (15%), "depression" (20% After each phase, participants were asked to rate pain intensity and perceived stress on visual analogue scales (VAS) with outcomes ranging from "No pain" for "very intense pain" and "not at all" for "very stressed", respectively.

Pain
There was reduced skin conductance and muscle tension compared to the control, which led to regulation of pain parameters. Diastolic pressure in FM patients tends to be reduced, and was regularized with therapy.  The study showed that the most significant result of CBT was the improvement in self-efficacy, which contributes to more favorable health behaviors such as exercise, relaxation training, and the continuous practice of adaptive coping strategies. Ang  PGIC questionnaire and the 1) Beck Depression Inventory 2) Spielberg Anxiety Inventory 3) weekly pain intensity 4) thresholds from pain to pressure before and after treatment. Functional Magnetic Resonance was also used as a parameter.
CBT in FM patients was associated with increased activity of the ventrolateral prefrontal cortex and orbitofrontal cortex during evoked pain, which are involved in executive cognitive control. CBT has also been associated with reductions in depression and anxiety.  gree of connectivity between areas of the cerebral cortex related to pain [32].
Some clinical outcomes observed significant associations between changes in brain connectivity and long-term gains [32]. There was less pain sensation and improved resistance in those patients who underwent CBT [30], and more than half of the participants achieved declines in pain scales. Results indicate that CBT contributes to shifts in pain processing, promoting considerable improvement in clinical distress over time [27].
Few studies have not shown an improvement in the clinical status of patients.
Falcão et al. (2008) [37] observed that patients who underwent CBT reduced the use of analgesics, but without objectively improving pain. Plasma levels of neuropeptide substance P (related to pain and stress signaling) in women with fibromyalgia who underwent CBT were reduced by 33%. However, there were no changes in the patients' state, and in some cases, the pain was considered even more significant after treatment with CBT [16]. CBT did not improve pain compared to control. However, there were immediate and clinically meaningful pain reductions in one-third of patients in both groups analyzed [15].

Fatigue and Insomnia
The study by Lera et al. (2009) [24] observed that the association of CBT and multidisciplinary treatment was only effective in patients with chronic fatigue.

Cost-Effectiveness of Treatment
CBT is cost-effective when compared to pharmacological treatment (pregabalin + duloxetine), usual care groups, and FDA-recommended drugs [19].

Well-Being
CBT and pharmacological therapy have the potential to relieve FM symptoms.
The first was superior in regards to anxiety and depression [20] [31] [37]. In addition, it improved the perception of clinical symptoms through an alteration of afferent pain signals, emotions, cognitions and anxiety reduction, with a significantly greater subjective impression of clinical improvement compared to controls [27]. Open Journal of Rheumatology and Autoimmune Diseases CBT has been related to an improvement in quality of life in general, facilitating daily activities due to a decrease in functional limitation and improvement in morning stiffness [20] [22] [39].
In the study by Gelman et al. (2002) [13] it was achieved a better coexistence with pain and a better adaptation and acceptance of the disorder and, therefore, a better quality of life with the learning of cognitive-behavioral coping strategies in the group of patients who did CBT. Accepting the disease and managing stress are valuable tools for improving the quality of life. Additionally, patients in the CBT group had a positive effect on "life control" which was maintained 12 months after the start of treatment [35].
The study by Jensen et al. (2012) [27] evaluated the effect of cognitive-behavioral therapy on the cortical activation of the CNS through functional magnetic resonance in patients with FM. There was evidence of increased activation in the ventrolateral prefrontal cortex, responsible for executive cognitive control. In the clinical setting, the patients treated with CBT exhibited improvement in symptoms of depression and anxiety.

Medications, Comparison, and Association with CBT
When comparing CBT and pharmacological therapy in FM, CBT was proved to be superior, resulting in improved quality of life, reduced catastrophizing, and better pain acceptance [25]. Combined therapy improved pain, quality of life, and perception of social support compared to pharmacological therapy alone [21] [28] [31].
On the other hand, Garcia et al. (2006) [22] argues that CBT therapy associated with medications has not shown increased efficacy, and CBT alone would be more effective. The use of CBT for a limited time seems to be more effective and lasting than continuous pharmacological management, considering the side effects and the long-term cost [14] [22].
Patients in CBT had a lower rate of depression and higher scores in mental health compared to patients who used only pharmacological therapy, in addition to reducing the weekly use of acetaminophen for pain control. However, pharmacological therapy and CBT have shown similar results when dealing with symptoms of pain, anxiety, and quality of life [37].

Other Non-Pharmacological Therapies and CBT
Patients undergoing CBT in association with hypnosis showed significant improvement in the FIQ Total Score, a scale that assesses the impact of fibromyalgia (3.84, p < 0.01). There was a significant impact in patients undergoing CBT on the FIQ Total Score (t = 2.28; p < 0.05) [17].
CBT was more effective than pharmacological therapy in improving pain, stiffness, the number of tender points, catastrophizing, emotional stress, and sleep. The joining of hypnosis and CBT was even more effective [18]. Multidisciplinary therapy has led to better living with pain and better adaptation and acceptance in the short and long term [13]. Open Journal of Rheumatology and Autoimmune Diseases The treatment effects of a combination of physical exercise and CBT in high-risk FM were significant for all primary outcomes, showing differences in physical (pain, fatigue, and functional disability) and psychological (negative mood, anxiety, and autonomy) functioning [33] [38].
On the other hand, Redondo et al. (2004) [23], also observed short-term clinical improvement, but without significant improvement one year after treatment. Exercise in association with motivational therapy increased physical capacity and improved clinical outcomes in patients who did not regularly use opioids. The study by Lera et al. (2009) [24] observed that the association of CBT with multidisciplinary treatment was only effective in patients with chronic fatigue. In other patients, only multidisciplinary treatment was effective in improving the clinical picture.

Conclusions
Cognitive Behavioral Therapy (CBT) has a great impact on the quality of life of patients, improving pain and fighting depression, anxiety, stress, rigidity, fatigue, and insomnia associated with the condition, facilitating daily activities and reducing functional limitations. Such improvement is maintained for a prolonged period after the end of treatment.
In addition to the monotherapeutic use, CBT can be associated with physical exercise, relaxation, psychological treatment, and hypnosis, presenting synergistic effects with each other.
CBT, despite being more cost-effective and more effective compared to drug therapy, can be used concomitantly with the latter, with analgesics and antidepressants being the most frequently used in the treatment.