Search Results (32)

Introduction: Vaccination against COVID-19 has been crucial in controlling the pandemic. While side effects are typically mild, rare neurological complications have been reported. This is a case series of ten patients who reported of persistent fasciculations after COVID-19 vaccination. Methods: We describe the clinical presentation and diagnostic work-up of ten patients with new-onset fasciculations in temporal proximity to COVID-19 vaccination. Patients with prior SARS-CoV-2 infection or known alternative causes of fasciculations were excluded. Routine clinical data, including neurological examination, laboratory results, and electrophysiology (electromyography and nerve conduction studies), were analyzed. Results: Ten patients (5 male, 5 female; mean age 42.4 years) reported fasciculations beginning within 6 h to 13 days post-vaccination and persisting for 2–12 months at the time of presentation. Fasciculations were accompanied by additional symptoms such as paresthesia and fatigue. Laboratory results were mostly unremarkable; two patients had positive myositis antibodies without clinical correlates. Electrophysiology was unremarkable in six patients, while fasciculation potentials were detected in four patients. Nine were diagnosed with probable benign fasciculation syndrome (BFS), and one met diagnostic criteria for amyotrophic lateral sclerosis (ALS). Discussion: In this small, retrospective case series, most cases of post-vaccination fasciculations were benign and compatible with BFS. Whether BFS onset was causally linked to vaccination or due to a nocebo effect remains unclear. One patient was diagnosed with ALS, though a causal link remains speculative given the study’s limitations and rarity of similar reports. Larger, prospective studies are needed to validate these observations and explore underlying pathophysiological mechanisms. Full article

Background and Objectives: Muscle symptoms are the most visible adverse event attributed to statins, but terminology is often imprecise. Most patients report myalgia or nonspecific aches, whereas objective myopathy, inflammatory or necrotizing myositis, rhabdomyolysis, and anti-HMGCR immune-mediated necrotizing myopathy are uncommon and clinically distinct entities. To provide a clinically oriented narrative synthesis of statin-associated muscle symptoms (SAMS) and severe statin-associated myotoxicity, and to propose a practical prevention, evaluation, and management algorithm. The classification of muscle events is used to standardize terminology and avoid diagnostic confusion, not to create a new formal taxonomy. Materials and Methods: A clinically oriented narrative review was performed using PubMed, Google Scholar, and major society documents published from January 2021 to April 2026. Eligible sources addressed SAMS, statin myopathy/myositis, rhabdomyolysis, anti-HMGCR immune-mediated necrotizing myopathy, nocebo/drucebo effects, pharmacogenetics, drug interactions, diagnosis, or management. The final evidence set comprised 55 verifiable sources, including blinded randomized or n-of-1/crossover evidence; meta-analyses; clinical statements and reviews; pharmacovigilance analyses; pharmacogenetic guidance; mechanism-focused reviews; anti-HMGCR series; and lipid-lowering guideline/treatment studies. Because the review was narrative, no pooled estimate or formal PRISMA screening log was generated. Results: Blinded evidence indicates only a small absolute excess of muscle pain with statins, concentrated mainly in the first year of therapy, and that most muscle symptoms reported during statin therapy are not pharmacologically caused by the statin. N-of-1 and crossover trials show that symptom intensity is often similar during statin and placebo periods, consistent with an important nocebo/drucebo contribution. Severe muscle toxicity can nevertheless occur, especially when systemic statin exposure is increased by a high dose, interacting drugs, frailty, renal or hepatic impairment, hypothyroidism, transporter or metabolic genotypes, or intense unaccustomed exercise. Statin choice matters chiefly through dose, pharmacokinetics, and interaction burden. Conclusions: SAMS are common as reported clinical problems, but confirmed statin-caused muscle injury is substantially less frequent than routine clinical attribution suggests. Permanent discontinuation should be reserved for carefully assessed cases. A structured approach—baseline risk assessment, selective CK measurement, exclusion of alternative causes, correction of modifiable risks, dechallenge/rechallenge, statin switching, dose reduction, and combination with non-statin therapy—preserves cardiovascular benefit while protecting the rare patient with genuine toxicity. Full article

Background: Nocebo effects are described as adverse symptoms arising from negative expectations rather than direct physiological harm, and are increasingly recognised across healthcare. While traditionally examined within pharmacological trials, emerging literature suggests that nocebo effects are shaped by broader interactional, situational, and communicative processes. In dentistry and paediatric care, where behaviour support and reassurance are central to practice, these mechanisms remain under-synthesised. Objectives: This scoping review aimed to map how nocebo effects are conceptualised across healthcare literature, with particular attention to the role of communication, reassurance, and behaviour support, and to explore how these mechanisms are discussed in paediatric, procedural, and dental contexts. Methods: An interpretive scoping review was conducted in line with JBI guidance and PRISMA-ScR reporting standards. Multidisciplinary literature spanning experimental, clinical, ethical, and applied domains was systematically identified and charted. Studies were grouped using a conceptual framework encompassing expectancy, learning, communication-mediated, ethical, and contextual mechanisms, allowing overlap between categories. Results: A large and heterogeneous body of literature was identified, with most studies conceptualising nocebo effects through overlapping mechanisms rather than discrete pathways. Expectancy and learning processes formed a foundational substrate across contexts, while communication, including framing, tone, reassurance, and checking-in, emerged as an active mechanism shaping symptom perception and vigilance. Ethical discussions highlighted tensions between transparency and potential harm, particularly in consent and risk communication. Paediatric and procedural settings, including dental sedation, were comparatively underrepresented despite features likely to amplify nocebo effects, such as reduced agency and heightened attentional focus. Conclusions: Nocebo effects are best understood as interactional phenomena that emerge within everyday clinical encounters. This review highlights the need to critically examine behaviour support practices, including reassurance, that are typically assumed to be benign. Greater conceptual clarity and reflexivity in communication may support future research and training aimed at minimising unintended distress within dental and paediatric care. These findings suggest that routine communication practices, including reassurance and expectation-setting, should be understood as active components of care that can influence patient experience, rather than as neutral or purely supportive interactions. Full article

The perception that hormonal contraception causes weight gain is a general belief that frequently hinders the initiation and continuation of effective family planning. This narrative review analyses data from Cochrane systematic reviews and recent pharmacogenomic studies to separate patient perception from metabolic reality. Analysis of high-quality data, including Cochrane systematic reviews, indicates that the association between Combined Hormonal Contraceptives (CHCs)—including oral pills, the transdermal patch, and the vaginal ring—and weight gain is not supported by consistent high-quality evidence. Placebo-controlled trials demonstrate that these methods are weight-neutral on average. Perceived weight increases in CHC users are likely mediated in part by fluid retention linked to the estrogenic stimulation of the Renin–Angiotensin–Aldosterone System (RAAS), rather than adipose tissue accumulation. Conversely, Depot Medroxyprogesterone Acetate (DMPA) represents a verified clinical risk for weight gain, showing a demonstrated clinical association with significant fat mass accumulation. Hypothesized biological mechanisms for this increase include hypothalamic appetite stimulation and glucocorticoid-like activity. The etonogestrel implant occupies a complex middle ground. While population-level data suggests weight neutrality, recent exploratory pharmacogenomic research has identified a specific variant in the Estrogen Receptor 1 (ESR1) gene. For the minority of women carrying this variant, the implant may trigger clinically significant weight gain, suggesting a biological basis for their subjective experience despite statistical evidence. Ultimately, the persistence of the weight gain concern is fueled by the nocebo effect and the misattribution of natural age-related weight trajectories to contraceptive use. Full article

Placebo, nocebo, and lessebo effects are very frequent in patients with both neurological and psychiatric disorders. Interestingly, the neural mechanisms underlying placebo effects have been found to be the same as or similar to mechanisms targeted by active pharmaceutical interventions for many of these disorders. In the case of functional neurological disorders (FNDs), there are shared neural substrates between the central nervous system “placebo network” and the dysfunctional networks implicated in the pathophysiology. These networks are primarily involved in emotion regulation, stress responses, and the sense of self-agency. Therefore, placebo effects have also been discussed as therapeutic interventions in FNDs. Such an approach, however, has a variety of ethical implications evolving around informed consent, autonomy, nonmaleficence, beneficence, and justice. In this paper, we discuss the use of placebo, nocebo, and lessebo in FNDs as well as related ethical issues. Overall, the use of placebo in FNDs is currently still considered controversial both for diagnostic as well as therapeutic purposes. Although it is a safe and almost unique intervention, its use violates the core principles of medical ethics and doctor–patient interactions involving autonomy or openness in the therapeutic relationship. Full article

Threat activation or deactivation in the brain–body is associated with learned nocebo or placebo somatic effects induced by fake invasive medical–surgical procedures. Some functional somatic disorders (FSDs) originate as acute nocebo somatic effects and can become 30–50% of chronic somatic presentations to primary care physicians. Patients with FSD overutilize medical–surgical services, despite the lack of identified pathophysiology, and are at risk for morbidity from unintentional iatrogenic injury. The Conditioned Response Model (CRM) of learning postulates three innate mechanisms, modulated by trait hypnotizability, which drive placebo and nocebo somatic effects and FSD. The High Risk Model of Threat Perception (HRMTP) postulates 10 psychosocial risk factors that modulate threat perception, driving placebo and nocebo somatic effectsandbiologically embedded FSD. Psychosocial factors and the trait of high and low hypnotizability modulate threat and are postulated to reduce heart rate variability(HRV), inducing autonomic nervous system(ANS)dysregulation. Reduced HRV was found in a large (N = 6,891) sample of patients with FSD. A total of 50% of patients with FSD with chronic pain (n = 224) without identified pathophysiology had a Paradoxical Increase in hand Temperature (PTI) during experimental threat induction. The HRMTP predicts that PTI associated with ANS dysregulation is associated with the risk factor Adverse Childhood Experiences (ACEs). This ACE prediction was independently confirmed. Learning predicts that threat activation by unconscious neutral stimuli (CS) can amplify nocebo and FSD and can negate placebo effects in clinician–patient relationships. Identifying psychosocial risk factors that modulate threat perception enables the diagnosis of FSD by inclusion and not simply by excluding pathophysiology. Full article

Irritable bowel syndrome (IBS) is a gut–brain axis chronic disorder, characterized by recurrent abdominal pain and altered bowel habits in the absence of organic pathology. Nutrition plays a central role in symptom management, yet no single dietary strategy has demonstrated universal effectiveness. This narrative review critically evaluates current nutritional approaches to IBS. The low-Fermentable Oligo-, Di-, Mono-saccharides and Polyols (FODMAP) diet is the most extensively studied and provides short-term symptom relief, but its long-term effects on microbiota diversity remain concerning. The Mediterranean diet, due to its anti-inflammatory and prebiotic properties, offers a sustainable, microbiota-friendly option; however, it has specific limitations in the context of IBS, particularly due to the adverse effects of certain FODMAP-rich foods. A gluten-free diet may benefit individuals with suspected non-celiac gluten sensitivity, although improvements are often attributed to fructan restriction and placebo and nocebo effects. Lactose-free diets are effective in patients with documented lactose intolerance, while a high-soluble-fiber diet is beneficial for constipation-predominant IBS. IgG-based elimination diets are emerging but remain controversial and require further validation. In this review, we present the 10 dietary commandments for IBS, pragmatic and easily retained recommendations. It advocates a personalized, flexible, and multidisciplinary management approach, avoiding rigidity and standardized protocols, with the aim of optimizing adherence, symptom mitigation, and health-related quality of life. Future research should aim to evaluate, in real-world clinical settings, the impact and applicability of the 10 dietary commandments for IBS in terms of symptom improvement and quality of life Full article

Patients’ attitude toward therapy and adherence to treatment are central in determining the long-term outcomes of medical treatment in ulcerative colitis. A complex interplay of differing factors modulates the likelihood of persisting in or discontinuing treatment, including patients’ beliefs and concerns about adverse effects of drugs, as well as the interactions with medical staff. Emotional attitude and expectancies are reflected in the so-called placebo and nocebo effects which influence patients’ choices to adhere to or discontinue treatment. They represent important confounding factors in clinical trials and are amplified when the evaluation relies on patient-reported outcomes more than on objective measurements. The therapeutic gain related to placebo effects is likely also relevant in day-to-day practice, but few data are available. The aim of the present narrative review is to provide critical insight into the adherence to therapy in ulcerative colitis and its interaction with the emotional component of the effects of therapy, resulting in the placebo/nocebo effects. Understanding the mechanisms underlying patient behavior may help identify the most appropriate therapeutic approach and treatment schedule to optimize adherence and outcomes in individual patients with UC. Full article

Background: The advent of biosimilars has revolutionized the management of conditions like rheumatoid arthritis by offering cost-effective alternatives to expensive biologics. Objectives: This study aims to compare the post-marketing safety profiles of biosimilars used in rheumatology with their respective reference products (RPs). Methods: Data were retrieved from EudraVigilance for biosimilars of adalimumab, etanercept, infliximab, and rituximab, and compared with their RPs. Our analysis focused on biosimilars authorized before 2021, using data from January 2021 to December 2023. We conducted a descriptive analysis of suspected adverse events, categorized using the Medical Dictionary for Regulatory Activities, and performed a comparative analysis using the reporting odds ratio to identify potential safety signals of disproportionate reporting. Results: We analyzed 75,327 reports, identifying 566,249 drug–event pairs. The results indicate that biosimilars have safety profiles largely comparable to their RPs. Female patients predominated in the reports, representing 69.4% of RPs and 56.9% of biosimilars. Notably, biosimilars demonstrated higher reporting rates for non-serious suspected adverse drug events (AEs), such as injection site pain, arthralgia, and fatigue. Specific AEs, including drug ineffectiveness and off-label use, were more frequent for infliximab and etanercept biosimilars, possibly reflecting real-world usage patterns and nocebo effects. Serious AEs, including malignancies and immunological reactions, were also noted, underscoring the necessity for ongoing monitoring. Conclusions: Our findings suggest that biosimilars are safe alternatives to RPs, contributing to significant healthcare cost savings in the EU. This study underscores the need for ongoing pharmacovigilance and long-term safety research to validate the clinical use of biosimilars in rheumatology. Full article

This retrospective study investigates botulinum toxin changes in 206 patients with spasticity, following reimbursement adjustments in France. The main objective was to evaluate the tolerance and efficacy of these changes, a topic underexplored due to the common practice of maintaining the same toxin brand. The majority of patients switched from Botox to Xeomin (73.66%), while others switched from Botox to Dysport (14.63%) or from Xeomin to Dysport (11.71%). Dose adjustments varied depending on the switch, with the change from Botox to Xeomin showing the greatest diversity in adjustments. Overall, tolerance was good, with few adverse effects reported, primarily fatigue. Perceived efficacy fluctuated, with some patients noting improvement while others experienced deterioration, but the median remained stable. A majority of patients (57.06%) chose to continue with their new treatment, indicating general satisfaction, though 42.93% preferred to return to their initial treatment. This study highlights the importance of an individualized approach and careful monitoring during toxin changes. The results suggest that toxin switches can be made without an increase in adverse effects. While differences between groups were observed, they were not statistically significant. Placebo and nocebo effects may influence perceptions of efficacy and side effects during treatment changes. Full article

Background: Nutritional expectations have been shown to influence exercise performance via placebo and nocebo effects. The present study aimed to evaluate performance-enhancement expectations for coffee and energy drinks using the Stanford Expectations of Treatment Scale. Methods: A total of 402 participants (48.5% male) with an average exercise history of 4.53 years, engaging in average physical activity 3.91 times per week, were included in the study. Data collection was conducted through the Qualtrics platform. Results: Participants exhibited significantly higher positive expectations for coffee compared to energy drinks (p = 0.002), whereas negative expectations were more pronounced for energy drinks than for coffee (p < 0.001). Males and individuals engaging in anaerobic exercise expressed more positive expectations for energy drinks than females and those participating in aerobic or mixed exercise regimens. Additionally, high-frequency exercisers (≥4 sessions per week) reported greater positive expectations for both beverages and fewer negative expectations for coffee than low-frequency exercisers (≤3 sessions per week). Correlational analyses revealed weak but significant associations between expectations and variables such as exercise history, frequency, intensity, and age. Conclusions: The findings suggest that coffee is perceived as a more effective performance enhancer and exhibits greater placebo-inducing potential than energy drinks, which may elicit stronger nocebo effects. These group-specific perceptions should be considered by trainers, coaches, and researchers when addressing placebo–nocebo mechanisms in the context of sports and exercise. Full article

Sports performance could be affected by placebo and nocebo effects. The last literature review on placebo and nocebo effects on sports and exercise performance was published in 2019. In the past five years, several new studies have been published. This review aimed to update the previous synthesis and evaluate the results of new studies focusing on placebo or nocebo interventions in sports and exercise by determining the form and magnitude of their effect. Hence, we searched for empirical studies published from 2019 until the end of May 2024 indexed in PubMed, Medline, Web of Science, EBSCO, and Google Scholar databases. The search yielded 20 eligible studies with control or baseline-control conditions, focusing on nutritional, mechanical, and other mixed ergogenic aids. They yielded small to large placebo effects (Cohen’s d) for nutritional (d = 0.86), mechanical (d = 0.38), cream and gel (d = 0.05), and open-label placebo (d = 0.16) interventions. The pooled effect size for placebo effects was moderate to large (d = 0.67), larger than in the earlier review, suggesting that placebo effects can improve motor performance even more than previously reported. However, based on five measures from three studies, the nocebo effects were almost twice as large (d = 1.20). Accordingly, the current findings support and expand the last review in the field by yielding additional support for placebo and nocebo effects in sports and exercise. Full article

(1) Background: In recent years, placebo and nocebo effects have been extensively documented in different medical conditions, including pain. The scientific literature has provided strong evidence of how the psychosocial context accompanying the treatment administration can influence the therapeutic outcome positively (placebo effects) or negatively (nocebo effects). (2) Methods: This state-of-the-art paper aims to provide an updated overview of placebo and nocebo effects on pain. (3) Results: The most common study designs, the psychological mechanisms, and neurobiological/genetic determinants of these phenomena are discussed, focusing on the differences between positive and negative context effects on pain in experimental settings on healthy volunteers and in clinical settings on chronic pain patients. Finally, the last section describes the implications for clinical and research practice to maximize the medical and scientific routine and correctly interpret the results of research studies on placebo and nocebo effects. (4) Conclusions: While studies on healthy participants seem consistent and provide a clear picture of how the brain reacts to the context, there are no unique results of the occurrence and magnitude of placebo and nocebo effects in chronic pain patients, mainly due to the heterogeneity of pain. This opens up the need for future studies on the topic. Full article

Vaccination against COVID-19 is one of the highly effective preventative strategies to reduce morbidity and mortality associated with COVID-19 infection. The rapid approval of COVID-19 vaccination due to the raging pandemic, media coverage, anti-vaccination groups, and concerns about adverse effects associated with vaccination has given rise to COVID-19 vaccine hesitancy. Current evidence suggests that psychosomatic and nocebo-related adverse effects account for a significant proportion of common adverse effects following COVID-19 vaccination. The most common adverse effects are headache, fatigue, and myalgia, which are highly prone to nocebo effects. In our review article, we discuss the role of psychosomatic and nocebo effects in COVID-19 vaccination-related hesitancy, predictors of such effects, and strategies to reduce vaccine hesitancy. General education regarding psychosomatic and nocebo effects and specialized education for at-risk populations may reduce psychosomatic and nocebo-related adverse effects following COVID-19 vaccination, ultimately reducing hesitancy. Full article

Background. Although biosimilars have been increasingly used over recent years, some concerns about a potential loss of efficacy and altered safety profile when switching from an originator to a biosimilar still exist. Interchangeability can be a challenge for dermatologists too. An extensive systematic review of published switching studies among originators and biosimilars was carried out in order to provide evidence regarding the effects derived from the switch in terms of efficacy and safety outcomes in real-life contexts. Results. Thirty-seven articles were included in this systematic review (14 studies related to adalimumab, 10 to etanercept, 12 to infliximab, and 1 each to adalimumab, etanercept, and infliximab). Studies were mainly carried out among European countries. Most of them were observational studies or register-based studies. The majority of studies enrolled patients diagnosed with psoriasis or psoriatic arthritis who underwent a single switch from the originator to the biosimilar. Overall, the studies’ results demonstrated that switching between adalimumab, etanercept, and infliximab originators and biosimilars is safe and effective in a real-life setting of patients with dermatological conditions. Only a few studies highlighted an increase in the risk of loss of efficacy as well as an increased rate of AEs, both of which were identified as the main causes of biosimilar discontinuation, probably associated with the well-known phenomenon of the nocebo effect. Conclusion. Switching from a biologic originator to its biosimilar is safe and effective. Only a few studies have evaluated the switch among biosimilars; thus, no firm conclusion can be drawn for this type of switch in terms of the efficacy and safety outcomes. Based on our results, we believe that biosimilars can be considered interchangeable with their reference products and that no additional switch studies are necessary to support switching among originators and biosimilars in clinical practice. However, the continuous monitoring of all biologics (both originators and biosimilars) in routine clinical practice is strongly needed given their peculiar safety profile. Full article