Pharmacological Treatment of Fibromyalgia Syndrome: A Practice-Based Review.

PURPOSE OF REVIEW: Fibromyalgia Syndrome (FMS) is a complex chronic pain condition characterized by widespread musculoskeletal pain and numerous other debilitating symptoms. The purpose of this review is to provide a comprehensive overview, based on everyday clinical practice, of the drugs presently employed in the treatment of FMS. RECENT FINDINGS: The treatment of FMS is based on a multimodal approach, with pharmacologic treatment being an essential pillar. The drugs used include tricyclic antidepressants, serotonin and noradrenaline reuptake inhibitors, other antidepressants, anticonvulsants, myorelaxants, and analgesics. The effectiveness of these medications varies, and the choice of drug often depends on the specific symptoms presented by the patient. Many drugs tend to either address only some domains of the complex FMS symptomatology or have a limited effect on pain. Each treatment option comes with potential side effects and risks that necessitate careful consideration. It may be beneficial to divide patients into clinical subpopulations, such as FMS with comorbid depression, for more effective treatment. Despite the complexities and challenges, the pharmacological treatment remains a crucial part for the management of FMS. This review aims to guide clinicians in prescribing pharmacological treatment to individuals with FMS.

Fibromyalgia: one year in review 2023.

Fibromyalgia (FM) is a chronic syndrome characterised by widespread pain that affects millions of people worldwide. This article discusses various aspects of FM described in scientific papers published in 2022 and indexed in the PubMed database, including the most recent diagnostic acquisitions (especially in relation to the juvenile form of FM), risk factors, co-morbidities and objective measures. Emphasis is placed on the importance of identifying FM early and improving diagnostic methods (e.g. physical measurements, including walking test performance, hand grip force, and autonomic tests). The article also considers hypotheses concerning the pathophysiology of FM, including the role of inflammation, gut dysbiosis, and neuroinflammation, and possible treatment options, including medications such as antioxidants and kinin antagonists, neurostimulation, and mind-body interventions. Although ketamine, vitamin D, and hormone therapy have shown promise in reducing FM symptoms, further research is needed to optimise their use. Neurostimulation techniques, such as transcutaneous electrical nerve stimulation, transcranial direct-current stimulation and transcranial magnetic stimulation, have been investigated in terms of their efficacy in reducing pain and improving the quality of life. Finally, the role of nutrition is discussed as study findings suggest that weight control, modified high-antioxidant diets, and nutritional supplementation can help to alleviate the symptoms of FM.

Cardiovascular Risk Factors and Events in Fibromyalgia Patients.

BACKGROUND: Several studies have shown that patients with fibromyalgia present with neuroendocrine, inflammatory, and coagulation features linked to cardiovascular disease development. However, the exact profile of cardiovascular risk factors and events in fibromyalgia remains to be defined. OBJECTIVES: To compare the profile of cardiovascular risk factors and events between fibromyalgia outpatients and the general population in Italy. METHODS: Cardiovascular risk factors and events in fibromyalgia females were collected using the criteria adopted in the CUORE Project. RESULTS: The study comprised 62 female fibromyalgia patients and 4093 female controls from 35 to 75 years of age. The prevalence of hypertension, diabetes, atrial fibrillation, transient ischemic attack, and cardiovascular total burden was significantly higher in fibromyalgia females than in the general Italian population. No difference was found in blood fasting glucose, triglycerides, total and fractionated cholesterol levels, body mass index, and metabolic syndrome (MetS). The MetS rate was underestimated for methodological aspects. CONCLUSIONS: Fibromyalgia is associated with an increased cardiovascular burden, probably through a specific risk factor profile.

Onset and temporal sequencing patterns of comorbidity between lifetime major depression, panic disorder and fibromyalgia.

OBJECTIVES: Fibromyalgia (FM) is a syndrome of unknown aetiology characterised by chronic widespread musculoskeletal pain and associated with high rates of psychiatric comorbidities, mainly mood and anxiety disorders.This study aims to determine the age at onset (AAO) and temporal sequencing patterns of FM and its frequent and distinguishable psychiatric comorbidities, the major depressive episode/s (MDE), and panic disorder (PD). METHODS: Diagnosis of MDE and PD were assigned using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV). The AAO of FM, MDE, and PD was defined using the event history calendar. All patients completed a sociodemographic data form, self-report questionnaires measuring FM-related symptoms and function, and the Childhood Trauma Questionnaire-28 (CTQ-28). RESULTS: 98 (83%) of the 118 recruited patients with FM had at least one psychiatric comorbidity. Two main temporal patterns were identified among the 83 patients (70.3 %) who could reliably report the age at onset of FM and psychiatric comorbidities. In the concurrent comorbidity pattern (CCP), MDE and/or PD co-occurred with the onset of FM. In the sequential pattern (SP), the patients first developed PD, then MDE, and finally FM. FM patients with SP are overweight and younger than those with a CCP (FM concurrent with MDE and PD) and reported more childhood adversities, mainly sexual abuse. AAO of psychiatric comorbidities significantly differed between the two patterns. CONCLUSIONS: The presence of different temporal comorbidity patterns may suggest prevention/early treatment interventions, especially in patients with childhood adversities and early-onset PD.

Sociodemographic factors in fibromyalgia: results from the Italian Fibromyalgia Registry.

OBJECTIVES: Fibromyalgia (FM) is a chronic musculoskeletal pain syndrome of unknown aetiopathogenesis. Its development and maintenance are related to the interplay of biological, psychological, and contextual factors. Among the contextual factors, sociodemographic aspects are poorly elucidated. This study aimed to evaluate the relationships between sociodemographic/clinical factors and symptom severity measures using a web-based registry of patients with FM. METHODS: Adult patients with an ACR 2010/2011 diagnosis of FM underwent a clinical evaluation and were asked to complete questionnaires covering their sociodemographic data (gender, age, marital status, educational level), and disease-specific measures (the revised Fibromyalgia Impact Questionnaire (FIQR), and the Polysymptomatic Distress Scale (PDS)). RESULTS: Data relating to 3,221 patients (3001 women and 220 men) was collected. The ANOVA showed significant difference in mean FIQR scores when the five marital conditions (cohabiter, married, separated/divorced, single, widowed) were compared (F 3.321, p<0.01). While males and females were found to have comparable FIQR scores, the interaction between gender and marital status indicated that separated/divorced males have higher FIQR scores (F 5.684, p=0.001). The multiple regression analysis demonstrated that patients who reported lower educational level experienced more severe FM symptoms, as scored with FIQR (p<0.0001). CONCLUSIONS: Our results indicated that being male and separated/divorced is associated to higher severity of FM symptoms, as rated with FIQR. Furthermore, a relationship between educational level and FIQR scores has been detected. This study supports the importance of collecting simple SES measures to identify environmental risk factors for FM severity.

One year in review 2021: fibromyalgia.

Fibromyalgia (FM) is a syndrome of unknown aetiology characterised by chronic pain, fatigue, and disturbed sleep. This review presents and summarises the 2020 literature on FM by retrieving all articles indexed in PubMed between 1 January 2020 and 31 December 2020. The attention of the scientific community towards FM is constantly growing, and this year's review is focused on the diagnostic, pathogenetic and therapeutic aspects of this syndrome. In particular, the treatment options for FM, both pharmacological and non-pharmacological, have been extensively studied.

Hyperbaric oxygen therapy in fibromyalgia and the diseases involving the central nervous system.

OBJECTIVES: This paper briefly describes the therapeutic mechanisms underlying hyperbaric oxygen therapy (HBOT), and reviews data concerning its effects and efficacy in Parkinson's disease (PD) and fibromyalgia (FM). METHODS: The studies included in this review all evaluated the effect of HBOT in patients with diseases involving CNS. The PubMed databases were searched from 1980 to September 2019 using the keywords: 'hyperbaric oxygen therapy', 'fibromyalgia' and 'Parkinson's disease'. RESULTS: HBOT is already indicated in various diseases and is the subject of continuous research and development. Data from models of PD show that it may play a neuroprotective role because of its ability to reduce oxidative stress and neurodegeneration, and protect against neuronal apoptosis. It is effective in improving the symptoms and quality of life of fibromyalgia patients, and rectifies abnormal brain activity in pain-related areas. Evidence from animal studies supports its use as an alternative treatment for other rheumatic diseases as it alleviates pain and reduces inflammation. CONCLUSIONS: Data mainly from animal studies support the use of HBOT in the treatment of PD and rheumatic diseases, but further work is necessary to clarify its therapeutic role in patients with these chronic disorders.

Personalized Clinical Approaches to Anxiety Disorders.

Anxiety disorders (ADs) are common psychiatric disorders, with a lifetime prevalence estimated at 33.7% in epidemiological studies. ADs are associated with serious disability and severe impairment in quality of life. Although several treatments [e.g. selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs), pregabalin, tricyclic antidepressants and benzodiazepines and/or cognitive-behaviour therapy (CBT)] are recommended, a large number of patients (i.e. from 30 to 70%) do not achieve complete remission. According to the novel paradigm of personalized medicine, the search of possible predictors of both disease vulnerability and treatment response might be the best way to prevent more accurately disease risk and to tailor the most effective treatment for each individual. Although a growing body of studies have proposed several endophenotypes/markers (i.e. neurochemical, neuroimaging, physiological, genetic and epigenetic endophenotypes/markers) as possible predictors of ADs susceptibility and/or treatment response, findings are not robust enough to be considered acceptable to incorporate in the clinical practice. In order to obtain more reliable results, larger studies with a multimodal approach, based on a combination of different biomarkers, are needed.

Fibromyalgia and the concept of resilience.

The concept of resilience varies according to the context in which it is used. Resilience is broadly defined as a protective factor that makes people less vulnerable to future adverse life events, in this implying the previous occurrence of an adverse event that has to be confronted before individual equilibrium can be restored. This definition can be applied to fibromyalgia and other chronic pain situations. Resilience is profoundly related to reaction to acute or chronic stress, and is therefore involved in the stress response system. Corticotropin-releasing factor can be considered a fundamental biological element of resilience, which also involves neural mechanisms such as the hypothalamic-pituitary-adrenal (HPA) axis, the locus coeruleus/norepinephrine system, the mesolimbic reward circuit and the fear circuit. Resilience also has a genetic basis: certain genetic characteristics, affect the degree of vulnerability to chronic stress. The number of psychiatric symptoms in healthy adults with high resilience scores do not change when they are exposed to stressing life events, whereas less resilient people develop additional symptoms. This is a typical clinical feature of fibromyalgia. Although resilience could be a therapeutic target for any chronic pain condition, it is an under-developed area of research, particularly in the light of the emerging interactions of positive emotions, physical health, and changes in pro-inflammatory cytokine levels. Given the lack of any pharmacological treatment capable of controlling more than 30-50% of the cases of chronic pain, there is a need to discover new therapeutic targets and strategies capable of changing a non-resilient phenotype into a more resilient phenotype, especially in the case of chronic pain conditions that cannot be explained by a lesion or a disease affecting the somatosensory system. This holds true of fibromyalgia, which is characterised by a complex combination of positive signs and symptoms that vary enormously from person to person depending on a wide range of pathophysiological changes in which genotype and, more importantly, environmental factors may play a major role in developing a more or less resilient personality.

Hyperbaric oxygen treatment of fibromyalgia: a prospective observational clinical study.

OBJECTIVES: Fibromyalgia (FM) is a syndrome of unknown aetiology that is characterised by widespread musculoskeletal pain, fatigue and disordered sleep, and often associated with neuropsychiatric and cognitive symptoms. Current treatment options are only partially effective, but hyperbaric oxygen therapy (HBOT) seems to be capable of relieving some of the symptoms. The aim of this study was to evaluate the efficacy and safety of HBOT after fewer sessions than generally used, chosen on the basis of pre-clinical and clinical data showing its rapid and sustained antinociceptive effect. METHODS: Patients with FM underwent HBOT (100% oxygen at 2.5 ata with air breaks) administered on three days per week for a total of twenty 90-minute sessions. Pain, fatigue, the quality of sleep, symptoms of anxiety and depression, and the patients' health-related quality of life were prospectively assessed before and after ten and twenty sessions. RESULTS: Twenty-eight of the 32 study patients completed the 20 HBOT sessions. Pain scores and the symptoms of anxiety (but not those of depression) significantly improved after both 10 and 20 sessions, whereas fatigue and FM symptom severity scores significantly improved only after 20 sessions. There was no significant change in the quality of sleep. The adverse effects were limited. CONCLUSIONS: These findings support the view that HBOT is an effective, rapid and safe means of treating various symptoms of FM.

Features of mood associated with high body weight in females with fibromyalgia.

BACKGROUND: Fibromyalgia (FM) is a common syndrome whose main characteristic is chronic widespread musculoskeletal pain, the severity of which is frequently worsened by concomitant obesity. Major depression (MD), particularly as part of a bipolar spectrum disorder (BSD), is associated with both obesity and FM. OBJECTIVE: To evaluate the relationship between lifetime MD, hypomanic symptoms and the body mass index (BMI) in patients with FM. METHOD: Of the 115 patients originally screened, 87 women with FM finally entered the study. Forty-nine patients (57%) had a lifetime diagnosis of MD, assessed by a structured clinical interview based on DSM-IV criteria, and four of them (4.6%) had a current MD episode. Lifetime hypomanic symptoms were measured by means of the self-rated Hypomania Checklist. According to the international criteria for BMI, FM patients were classified as under/normal-weight (61%), overweight (30%) and obese (9%). RESULTS: 62 patients (71.2%) with FM had a bipolar spectrum disorder (BSD). Thirty (48.3%) of them met criteria for bipolar II disorder, 32 (51,6%) for bipolar disorder NOS (18 FM patients with MD associated to sub-syndromal hypomanic syndrome and 14 with hypomanic syndrome without MD). No patient had a bipolar I disorder. Only one patient met the criteria for a major depressive disorder (MDD). There was no significant difference in mean BMI between the patients with and without a lifetime diagnosis of MD, but there was a positive association between the level of hypomanic symptoms and BMI values (p<0.009). When hypomania was considered categorically as hypomanic syndrome there was no significant effect on BMI. CONCLUSIONS: Our finding adds to previous evidence indicating that hypomanic symptoms are a central feature of FM. In the case of the early identification of high-level hypomanic symptoms, body weight should be closely monitored in order to prevent obesity and its detrimental impact on females with FM.

An update on emerging drugs for fibromyalgia treatment.

INTRODUCTION: Fibromyalgia (FM) is a chronic disorder whose symptoms of pain, fatigue, sleep disturbances and depression have a devastating effect on patients' lives as it limits their ability to engage in everyday working and social activities, and make it difficult to maintain normal relationships with family, friends and employers. None of the currently available drugs are fully effective against the whole spectrum of symptoms. The aim of this narrative review is to summarise the data relating to the new therapeutic options that have become available over the last few years. Areas covered: Increasing efforts by the pharmaceutical industry have led to the introduction of new investigational drugs and new formulations of older drugs, and studies have been carried out in order to investigate the possibility of using drugs that are currently used for other diseases. Expert opinion: Slight improvements in the health of FM patients treated with drugs targeting a range of molecular mechanisms have been observed, but there is still no single drug that is capable of offering substantial efficacy against all of the characteristic symptoms of FM. The identification of new and improved therapies for FM requires consideration of the heterogeneity of the condition, which suggests the existence of different patient subgroups, a relationship between central and peripheral aspects of the pathophysiology, and the need for combined treatment with drugs targeting multiple molecular mechanisms.

Childhood adversities in patients with fibromyalgia: are they related to comorbid lifetime major depression?

OBJECTIVES: Fibromyalgia (FM) is a syndrome of unknown aetiology that is frequently associated with depressive disorders, and childhood adversities (including maltreatment and parental loss) are frequently described in subjects with FM and depression. The aim of this study was to investigate the extent to which the high percentage of childhood adversities reported by patients with FM is related to FM itself or to a comorbid lifetime depressive disorder. METHODS: Ninety-four consecutive FM patients were assessed for lifetime major depression using the DSM-IVSCID-CV interview. Childhood maltreatment was investigated using the Childhood Trauma Questionnaire, and information relating to parental death or separation before the age of 18 years was collected by means of a semi-structured interview. The Zung Self-Rating Depression Scale, used as a quantitative measure of depressive symptoms, and the childhood adversity assessment were recorded at the same time. RESULTS: Sixty of the 94 FM patients (63.8%) were diagnosed as having a lifetime major depressive disorder. There were no significant associations between childhood parental loss, the presence/level of maltreatment, the occurrence of a lifetime major depression episode, and the Zung Self-Rating Depression Scale scores. CONCLUSIONS: The results of this study suggest that there is no association between childhood adversities and comorbid lifetime major depression in patients with FM. As it would be helpful to prevent the development of FM because of the high cost and limited efficacy of therapeutic interventions, childhood adversities may offer targets for primary prevention.

Is panic disorder associated with clinical severity of fibromyalgia? A preliminary study in a tertiary-care centre.

OBJECTIVES: To investigate the influence of panic disorder (PD) with/without agoraphobia on the clinical severity of fibromyalgia (FM). METHODS: Eighty-one patients with FM, among those consecutively referring to a tertiary-care setting, were included in this cross-sectional study. Psychiatric diagnoses were made by the structured clinical interview in accordance with the 4th-TR version of the diagnostic and statistical manual of mental disorders. The clinical severity of FM was measured by means of the following self-administered scales: Fibromyalgia Impact Questionnaire (FIQ), Fibromyalgia Assessment Status (FAS), Health Assessment Questionnaire (HAQ). RESULTS: A final sample of 66 females with FM with or without past PD was included in the analyses. The two groups did not significantly differ in age, years of education, length of illness or medication distribution. We did not find significant differences between the two groups in the FIQ and FAS scale scores, whereas subjects with FM and past PD showed significantly higher HAQ scale scores than those without past PD (p<.001). CONCLUSIONS: A history of PD in patients with FM increases the severity of functional impairment in performing a wide range of daily-life activities, as measured by the HAQ scale, with no effects on the severity of other clinical dimensions of FM. Potential underlying mechanisms and clinical implications will be discussed.

Long-Term Pharmacological Treatments of Anxiety Disorders: An Updated Systematic Review.

Many aspects of long-term pharmacological treatments for anxiety disorders (AnxDs) are still debated. We undertook an updated systematic review of long-term pharmacological studies on panic disorder (PD), generalized anxiety disorder (GAD), and social anxiety disorder (SAD). Relevant studies dating from January 1, 2012 to August 31, 2015 were identified using the PubMed database and a review of bibliographies. Of 372 records identified in the search, five studies on PD and 15 on GAD were included in the review. No studies on SAD were found. Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy. Paroxetine, escitalopram, and clonazepam can be effective for long-term treatment of PD. However, further studies are needed to draw conclusions about the long-term benzodiazepine use in PD, particularly for the possible cognitive side-effects over time. Pregabalin and quetiapine can be effective for long-term treatment of GAD, while preliminary suggestions emerged for agomelatine and vortioxetine. We did not find any evidence for determining the optimal length and/or dosage of medications to minimize the relapse risk. Few investigations have attempted to identify potential predictors of long-term treatment response. Personalized treatments for AnxDs can be implemented using predictive tools to explore those factors affecting treatment response/tolerability heterogeneity, including neurobiological functions/clinical profiles, comorbidity, biomarkers, and genetic features, and to tailor medications according to each patient's unique features.

Are Anxiety Disorders Associated with Accelerated Aging? A Focus on Neuroprogression.

Anxiety disorders (AnxDs) are highly prevalent throughout the lifespan, with detrimental effects on daily-life functioning, somatic health, and quality of life. An emerging perspective suggested that AnxDs may be associated with accelerated aging. In this paper, we explored the association between AnxDs and hallmarks of accelerated aging, with a specific focus on neuroprogression. We reviewed animal and human findings that suggest an overlap between processes of impaired neurogenesis, neurodegeneration, structural, functional, molecular, and cellular modifications in AnxDs, and aging. Although this research is at an early stage, our review suggests a link between anxiety and accelerated aging across multiple processes involved in neuroprogression. Brain structural and functional changes that accompany normal aging were more pronounced in subjects with AnxDs than in coevals without AnxDs, including reduced grey matter density, white matter alterations, impaired functional connectivity of large-scale brain networks, and poorer cognitive performance. Similarly, molecular correlates of brain aging, including telomere shortening, Aß accumulation, and immune-inflammatory and oxidative/nitrosative stress, were overrepresented in anxious subjects. No conclusions about causality or directionality between anxiety and accelerated aging can be drawn. Potential mechanisms of this association, limitations of the current research, and implications for treatments and future studies are discussed.

INTERSTITIAL LUNG DISEASE in RHEUMATIC DISEASES: AN UPDATE of the 2018 REVIEW.

INTRODUCTION: Interstitial lung disease (ILD) is a potential severe complication of various rheumatic diseases, typically connective tissue diseases (CTD), associated with significant morbidity and mortality. ILD may occur during the course of the disease but may also be its first manifestation. Several cell types are involved in ILD's pathogenesis, and if not controlled, pulmonary inflammation may lead to pulmonary fibrosis. AREAS COVERED: We searched PubMed, Medline, and the Cochrane Library for papers published between 1995 and February 2017 in the first version, and between 2017 and April 2023 using combinations of words. The most frequent systemic rheumatic diseases associated with ILD are systemic sclerosis (SSc), rheumatoid arthritis (RA), and idiopathic inflammatory myositis. Treatment and monitoring guidelines are still lacking, and current treatment strategies have been extrapolated from the literature on SSc and established treatments for non-pulmonary systemic rheumatic manifestations. EXPERT OPINION: Given the complexity of diagnosis and the paucity of treatment trials, managing CTD patients with ILD is challenging. It requires the skills of multidisciplinary CTD-ILD clinics including at least rheumatologists and lung specialists.