Pharmacological approaches to the management of panic disorder in older patients: a systematic review.

INTRODUCTION: Recommendations for treating panic disorder (PD) in older patients are scarce. The authors have systematically reviewed whether several recommended medications are superior to others and their optimal doses in this age group. METHODS: A database search of studies involving patients with PD with/without agoraphobia aged ≥ 60 years was carried out using PubMed, PsycINFO, Embase, and Clinical Trials.gov, from their inception dates to 1 March 2023. Only four (published from 2002 to 2010) of the 1292 records screened were included. A risk of bias assessment was provided. This systematic review was performed using The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). RESULTS: Two studies were randomized clinical trials, whereas two were open-label, including paroxetine, citalopram, escitalopram, and sertraline; three studies reported short-term evaluations, whereas one study included a 26-week follow-up. Medications provided benefits, with good tolerability. Preliminary results suggested greater benefits of paroxetine in reducing panic attacks vs. cognitive - behavioral therapy, and an earlier decrease in PAs with escitalopram vs. citalopram. Risk of bias was considerable. CONCLUSIONS: The pharmacological management of PD in older patients has received no attention. Findings are scant, dated, and affected by methodological flaws; thus, they do not provide significant advances.

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.

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 in Systemic Inflammatory Arthritis.

In recent years, several papers have been published on cardiovascular (CV) involvement, risk, management, and treatment in systemic inflammatory arthritis (SIA), including rheumatoid arthritis, (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) [...].

Cardiorespiratory Assessments in Panic Disorder Facilitated by Wearable Devices: A Systematic Review and Brief Comparison of the Wearable Zephyr BioPatch with the Quark-b2 Stationary Testing System.

Abnormalities in cardiorespiratory measurements have repeatedly been found in patients with panic disorder (PD) during laboratory-based assessments. However, recordings performed outside laboratory settings are required to test the ecological validity of these findings. Wearable devices, such as sensor-imbedded garments, biopatches, and smartwatches, are promising tools for this purpose. We systematically reviewed the evidence for wearables-based cardiorespiratory assessments in PD by searching for publications on the PubMed, PsycINFO, and Embase databases, from inception to 30 July 2022. After the screening of two-hundred and twenty records, eight studies were included. The limited number of available studies and critical aspects related to the uncertain reliability of wearables-based assessments, especially concerning respiration, prevented us from drawing conclusions about the cardiorespiratory function of patients with PD in daily life. We also present preliminary data on a pilot study conducted on volunteers at the Villa San Benedetto Menni Hospital for evaluating the accuracy of heart rate (HR) and breathing rate (BR) measurements by the wearable Zephyr BioPatch compared with the Quark-b2 stationary testing system. Our exploratory results suggested possible BR and HR misestimation by the wearable Zephyr BioPatch compared with the Quark-b2 system. Challenges of wearables-based cardiorespiratory assessment and possible solutions to improve their reliability and optimize their significant potential for the study of PD pathophysiology are presented.

Conventional, biological disease-modifying anti-rheumatic drugs and Janus kinase inhibitors and varicella zoster virus.

INTRODUCTION: The advent of biological disease-modifying anti-rheumatic drugs (bDMARDs), and more recently of Janus kinase inhibitors (JAKi), has had a major impact on the herpes zoster (HZ) reactivation, which represents an important clinical challenge in the treatment of inflammatory arthritis (IA) in patients with a complete pharmacological control of peripheral inflammation. AREAS COVERED: In this review, we provide an overview on the effects of conventional DMARDs/ bDMARDs and JAKi on HZ reactivation. Furthermore, we underline the controversial findings and the potential management strategies. We searched PubMed, Medline, and the Cochrane Library for papers published between 1995 and November 2022. EXPERT OPINION: The overall data showed a slightly higher risk of HZ in patients treated with bDMARDs, and more pronounced for those treated with JAKi. As management strategies, we suggest an effective vaccination campaign and a focus on early diagnosis.

High prevalence of major depression in US sleep clinics: the need for routine depression screening in sleep services.

Depression screening is not part of routine clinical practice in US sleep clinics. Our study aimed to report the prevalence of depression among individuals referred to US sleep clinics. According to our findings, approximately 21% of patients had depression, with about 4% reporting severe symptoms, 9% had frequent death and/or self-harming thoughts, and 61% were taking antidepressants. Our results highlighted a considerable risk of prevalent depression in sleep clinics and supported the limited existing data on this topic. Our study advocates for the need for routine depression screening in sleep services to reduce the detrimental consequences of a delayed depression diagnosis and the risk of a worse prognosis for both depression and sleep-wake disorders. CITATION: Daccò S, Caldirola D, Grassi M, Alciati A, Perna G, Defillo A. High prevalence of major depression in US sleep clinics: the need for routine depression screening in sleep services. J Clin Sleep Med. 2023;19(4):835-836.

Axial Spondyloarthritis: Reshape the Future-From the "2022 GISEA International Symposium".

The term "axial spondyloarthritis" (axSpA) refers to a group of chronic rheumatic diseases that predominantly involve the axial skeleton and consist of ankylosing spondylitis, reactive arthritis, arthritis/spondylitis associated with psoriasis (PsA) and arthritis/spondylitis associated with inflammatory bowel diseases (IBD). Moreover, pain is an important and common symptom of axSpA. It may progress to chronic pain, a more complicated bio-psychosocial phenomena, leading to a significant worsening of quality of life. The development of the axSpA inflammatory process is grounded in the complex interaction between genetic (such as HLA B27), epigenetic, and environmental factors associated with a dysregulated immune response. Considering the pivotal contribution of IL-23 and IL-17 in axSpA inflammation, the inhibition of these cytokines has been evaluated as a potential therapeutic strategy. With this context, here we discuss the main pathogenetic mechanisms, therapeutic approaches and the role of pain in axSpA from the 2022 International GISEA/OEG Symposium.

Effect of biological DMARDs and JAK inhibitors in pain of chronic inflammatory arthritis.

INTRODUCTION: The advent of biological disease-modifying anti-rheumatic drugs (bDMARDs) and, more recently, of Janus kinase inhibitors (JAKi) has had a major impact on the long-term outcomes of chronic inflammatory arthritis (IA). However, the persistence of pain, even in patients with a complete pharmacological control of peripheral inflammation, represents an important clinical challenge in the treatment of IA. AREAS COVERED: In this review, we provide an overview of possible mechanisms underlying pain in IA and its assessment, as well as the effects of bDMARDs and JAKi on pain management. EXPERT OPINION: The overall data showed a good effect of bDMARDs and JAKi on pain, which is more pronounced for JAKi. However, it is challenging to distinguish the effect on the different types of pain (nociceptive, neuropathic, and nociplastic).

Human-Induced Pluripotent Stem Cell Technology: Toward the Future of Personalized Psychiatry.

The polygenic and multifactorial nature of many psychiatric disorders has hampered implementation of the personalized medicine approach in clinical practice. However, induced pluripotent stem cell (iPSC) technology has emerged as an innovative tool for patient-specific disease modeling to expand the pathophysiology knowledge and treatment perspectives in the last decade. Current technologies enable adult human somatic cell reprogramming into iPSCs to generate neural cells and direct neural cell conversion to model organisms that exhibit phenotypes close to human diseases, thereby effectively representing relevant aspects of neuropsychiatric disorders. In this regard, iPSCs reflect patient pathophysiology and pharmacological responsiveness, particularly when cultured under conditions that emulate spatial tissue organization in brain organoids. Recently, the application of iPSCs has been frequently associated with gene editing that targets the disease-causing gene to deepen the illness pathophysiology and to conduct drug screening. Moreover, gene editing has provided a unique opportunity to repair the putative causative genetic lesions in patient-derived cells. Here, we review the use of iPSC technology to model and potentially treat neuropsychiatric disorders by illustrating the key studies on a series of mental disorders, including schizophrenia, major depressive disorder, bipolar disorder, and autism spectrum disorder. Future perspectives will involve the development of organ-on-a-chip platforms that control the microenvironmental conditions so as to reflect individual pathophysiological by adjusting physiochemical parameters according to personal health data. This strategy could open new ways by which to build a disease model that considers individual variability and tailors personalized treatments.

No Sex Differences in Self-Reported Childhood Maltreatment in Major Depressive and Bipolar Disorders: A Retrospective Study.

BACKGROUND: We investigated, for the first time, whether there are any sex differences in retrospective self-reported childhood maltreatment (CM) in Italian adult patients with major depressive disorder (MDD) or bipolar disorder (BD). Furthermore, the potential impacts of patients' age on the CM self-report were investigated. METHODS: This retrospective study used the data documented in the electronic medical records of patients who were hospitalized for a 4-week psychiatric rehabilitation program. CM was assessed using the 28-item Childhood Trauma Questionnaire (CTQ), which evaluates emotional, physical, and sexual abuse, as well as emotional and physical neglect. The linear and logistic regression models were used (α = 0.01). RESULTS: Three hundred thirty-five patients with MDD (255 women and 80 men) and 168 with BD (97 women and 71 men) were included. In both samples, considerable CM rates were identified, but no statistically significant sex differences were detected in the variety of CTQ-based CM aspects. There was a significant association, with no sex differences, between increasing patients' age and a decreasing burden of CM. CONCLUSION: Both women and men with MDD or BD experienced a similar and considerable CM burden. Our findings support routine CM assessment in psychiatric clinical practice.

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.

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.

First-onset major depression during the COVID-19 pandemic: A predictive machine learning model.

BACKGROUND: This study longitudinally evaluated first-onset major depression rates during the pandemic in Italian adults without any current clinician-diagnosed psychiatric disorder and created a predictive machine learning model (MLM) to evaluate subsequent independent samples. METHODS: An online, self-reported survey was released during two pandemic periods (May to June and September to October 2020). Provisional diagnoses of major depressive disorder (PMDD) were determined using a diagnostic algorithm based on the DSM criteria of the Patient Health Questionnaire-9 to maximize specificity. Gradient-boosted decision trees and the SHapley Additive exPlanations technique created the MLM and estimated each variable's predictive contribution. RESULTS: There were 3532 participants in the study. The final sample included 633 participants in the first wave (FW) survey and 290 in the second (SW). First-onset PMDD was found in 7.4% of FW participants and 7.2% of the SW. The final MLM, trained on the FW, displayed a sensitivity of 76.5% and a specificity of 77.8% when tested on the SW. The main factors identified in the MLM were low resilience, being an undergraduate student, being stressed by pandemic-related conditions, and low satisfaction with usual sleep before the pandemic and support from relatives. Current smoking and taking medication for medical conditions also contributed, albeit to a lesser extent. LIMITATIONS: Small sample size; self-report assessment; data covering 2020 only. CONCLUSIONS: Rates of first-onset PMDD among Italians during the first phases of the pandemic were considerable. Our MLM displayed a good predictive performance, suggesting potential goals for depression-preventive interventions during public health crises.

The association between body mass index and fibromyalgia severity: data from a cross-sectional survey of 2339 patients.

OBJECTIVE: Various studies have shown that overweight and obesity are central features of FM, but the real impact of a high BMI on clinical severity in patients with FM is still controversial. The aim of this study was to analyse the relationships between BMI categories and measures of symptom severity and functional impairment using data from a Web-based registry of patients with FM. METHODS: Adult patients with an ACR 2010/2011 diagnosis of FM underwent a complete physical examination and laboratory tests and were asked to complete a package of questionnaires covering their sociodemographic and treatment details, in addition to the following disease-specific questionnaires: the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromyalgia Assessment Status questionnaire (ModFAS) and the Polysymptomatic Distress Scale (PDS). RESULTS: A total of 2339 patients were recruited and divided into two weight categories, underweight/normal (U/N, n = 1127, 48.2%) and overweight/obese (O/O, n = 1212, 51.8%). The total and subscales of FIQR, ModFAS and PSD scores were significantly higher in the O/O patients, as were all the mean scores of the individual FIQR items (P < 0.001 for all). CONCLUSION: Our findings demonstrate that O/O patients with FM are significantly more impaired than U/N patients in all the symptomatological and functional domains as measured using the FIQR, ModFAS and PDS, thus suggesting that being O/O has an additional effect on symptoms and function.

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.

Experimental Drugs for Panic Disorder: An Updated Systematic Review.

Several effective pharmacological therapies for panic disorder (PD) are available, but they have some drawbacks, and unsatisfactory outcomes can occur. Expanding the variety of anti-panic medications may allow for improving PD treatment. The authors performed an updated systematic review of preclinical and clinical (Phase I-III) pharmacological studies to look for advances made in the last six years concerning novel-mechanism-based anti-panic compounds or using medications approved for nonpsychiatric medical conditions to treat PD. The study included seven published articles presenting a series of preclinical studies, two Phase I clinical studies with orexin receptor (OXR) antagonists, and two clinical studies investigating the effects of D-cycloserine (DCS) and xenon gas in individuals with PD. The latest preclinical findings confirmed and expanded previous promising indications of OXR1 antagonists as novel-mechanism-based anti-panic compounds. Translating preclinical research into clinical applications remains in the early stages. However, limited clinical findings suggested the selective OXR1 antagonist JNJ-61393115 may exert anti-panic effects in humans. Overall, OXR1 antagonists displayed a favorable profile of short-term safety and tolerability. Very preliminary suggestions of possible anti-panic effects of xenon gas emerged but need confirmation with more rigorous methodology. DCS did not seem promising as an enhancer of cognitive-behavioral therapy in PD. Future studies, including objective panic-related physiological parameters, such as respiratory measures, and expanding the use of panic vulnerability biomarkers, such as hypersensitivity to CO2 panic provocation, may allow for more reliable conclusions about the anti-panic properties of new compounds.