Expert Opinion on Pharmacotherapy最新文献

Introduction: Anorexia nervosa (AN) has one of the highest mortality rates of all mental illnesses. No approved pharmacological treatments exist for AN, but novel neurobiological targets show promise.

Areas covered: Studies show that in individuals with AN, there are alterations in brain neurotransmitter signaling, alongside associated mental rigidity and comorbid anxiety and depression. Available and new therapies could be used to improve alterations in neurobiology and behavior. This narrative review serves as a review of previously published literature assessing the efficacy of traditional pharmacotherapy in treating AN while also exploring novel treatments, including dissociative anesthetics, psychedelics, cannabinoids, hormones, neurosteroids, and ketogenic nutrition.

Expert opinion: If best practice psychotherapeutic interventions have failed, we recommend a neuroscience and brain research-based medication approach that targets dopamine neurotransmitter receptors to enhance cognitive flexibility and illness insight while reducing dread and avoidance toward food. It is furthermore essential to recognize and treat comorbid conditions such as anxiety, depression, or obsessive-compulsive disorder as they interfere with recovery, and typically do not resolve even with successful AN treatment. Novel strategies have the promise to show efficacy in improving mood and reducing specific AN psychopathology with hopes to be used in clinical practice soon.

Introduction: Mutation-specific disease modifying drugs such as the triple combination Elexacaftor/Tezacaftor/Ivacaftor (ETI), are associated with significant improvements in physical health. Reproductive health and a pursuit of parenthood are of increased relevance; a dramatic increase in childbirth rates for females with CF has already been observed.

Areas covered: Fertility in males and females with CF, and any subsequent impact of CFTR modulator therapy, is reviewed. The potential impacts of maternal use of CFTR modulator drugs on offspring health are considered, as constituent components have been found in fetal circulation in animals and humans, and the implications for maternal continuation or cessation of treatment. Clinical data are reassuring, although cases of lens opacities, and missed CF diagnoses due to false negative newborn screening results have been reported.

Expert opinion: More research and high-quality evidence are needed to characterize maternal, fetal and long-term offspring outcomes following CFTR modulator therapy use during pregnancy and breastfeeding. There is a potential therapeutic impact of targeting CFTR-related organ dysfunction in CF-fetuses via maternal-administration of CFTR modulators. Additionally, any consequences of CFTR-modulation in heterozygote carrier infant warrants urgent and collective consensus regarding ethical and clinical research programs to evaluate this discrete population.

Introduction: Liposarcomas are malignancies of adipocytic lineage and represent one of the most common types of soft tissue sarcomas. They encompass multiple histologies, each with unique molecular profiles. Treatment for localized disease includes resection, potentially with perioperative radiation or systemic therapy. Treatment for unresectable or metastatic disease revolves around palliative systemic therapy, for which improved therapies are urgently needed.

Areas covered: We reviewed the literature on novel therapies in clinical development for liposarcomas within the past 5 years and discuss their potential impact on future treatment strategies.

Expert opinion: Understanding of the molecular characteristics of liposarcoma subtypes has led to testing of several targeted therapies, including inhibitors of amplified gene products (CDK4 and MDM2) and upregulated proteins (XPO1). Immuno-oncology has played an increasing role in the treatment of liposarcomas, with checkpoint inhibition showing promise in dedifferentiated liposarcomas, and immune therapies targeting cancer testis antigens NY-ESO-1 and MAGE family proteins poised to become an option for myxoid/round cell liposarcomas. The search for novel agents from existing classes (tyrosine kinase inhibitors) with efficacy in liposarcoma also continues. Combination therapies as well as biomarker identification for patient selection of therapies warrant ongoing exploration.

Introduction: Pharmacological and other treatments for binge eating disorder (BED) predate its inclusion as the third main eating disorder in the 2013 DSM-5. Currently, second in line to psychological therapy are psychotropics such as antidepressants, anticonvulsants and stimulants.

Areas covered: This review summarizes the evidence and emerging evidence on the pharmacotherapies for BED and their potential for wider use.

Expert opinion: Pharmacotherapy has utility as an alternative or adjunctive treatment for those exhibiting insufficient response to, or not preferencing, psychological interventions. Medications may also benefit individuals with BED and other co-occurring mental health conditions, such as depression and attention deficit hyperactivity disorder. In addition, there are several agents (e.g. glucagon like peptide-1 receptor agonists and the combination of naltrexone-bupropion) displaying promise for weight and binge eating reduction in people with BED and high BMI. Future research should extend the understanding of the role of medication in BED, focusing on their sustained effects over time, when and if they may be ceased, their effectiveness in people with adequate weight, and the risks associated with weight loss in those with BED and high weight.

Introduction: Endometriosis affects 5% to 10% of reproductive age women and may be associated with severely painful and debilitating symptoms as well as infertility. Endometriosis involves hormonal fluctuations, angiogenesis, neurogenesis, vascular changes and neuroinflammatory processes. The neuroinflammatory component of endometriosis makes it a systemic disorder, similar to other chronic epithelial inflammatory conditions.

Areas covered: Inflammatory mediators, mast cells, macrophages, and glial cells play a role in endometriosis which can result in peripheral sensitization and central sensitization. There is overlap between chronic pelvic pain and endometriosis, but the two conditions are distinct. Effective treatment is based on a personalized approach using a variety of pharmacologic and other treatment options.

Expert opinion: Hormonal therapies are a first-line approach, but endometriosis is a challenging condition to manage. 'Add-back' hormonal therapy has been effective. Painful symptoms are likely caused by the interplay of multiple factors and there may be a neuropathic component. Analgesics and anticonvulsants may be appropriate. A holistic approach and multimodal treatments are likely to be most effective. In addition to pharmacologic treatment, there are surgical and alternative medicine options. Endometriosis may also have a psychological component.

Introduction: Gastroesophageal reflux disease (GERD) is a common debilitating chronic disease presenting in two main forms based on esophageal mucosal appearance, the erosive reflux disease (ERD) and the non-erosive reflux disease (NERD). Acid secretion is a key factor in the disease pathogenesis and management. Potent acid-suppressant drugs have been manufactured since the mid of 1970s, initially with histamine-H₂-receptors antagonists, and later, inhibitors of the proton pump (H⁺-K⁺-ATPase).More recently, potassium-competitive acid blockers (p-CABs), particularlyVonoprazan, have been introduced. Vonoprazan has shown high efficacy and safety profiles and exhibits several advantages that allow to overcome shortcomings of proton pump inhibitors (PPIs).

Areas covered: In this review, we provide an updated summary of Vonoprazan pharmacodynamics and its role in clinical practice for the management of erosive esophagitis and GERD-related heartburn. Moreover, we discuss characteristics of Vonoprazan that allow to bypass some limitations of the older PPIs.

Expert opinion: Long-term safety and efficacy of Vonoprazan have already been demonstrated for the induction and maintenance of ERD, preventing nocturnal acid breakthrough, reducing reflux symptoms in non-responder to standard therapy. Ongoing and future studies are expected to further elucidate its long-term benefits and potential applications in other acid-related disorders.

Introduction: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has been introduced as a superior term to describe steatosis on a background of metabolic dysregulation and is slated to become the leading cause of HCC worldwide, as the incidence of metabolic comorbidities is increasing. As such, MASLD has evolved into an important public health issue, potentially leading to higher rates of liver mortality and end-stage liver disease. To this end, understanding the association between MASLD and HCC may allow for the identification of better interventions and novel therapeutic strategies.

Areas covered: The authors provide a review of current knowledge on HCC development among patients with MASLD, with insights into molecular pathways and current and future therapeutic strategies.

Expert opinion: MASLD has a strong association with the risk of HCC development, as metabolic comorbidities induce dysregulation in molecular pathways, leading to insulin-resistance, oxidative stress, and chronic inflammation, thus causing progression to cirrhosis and eventually to HCC. Therapeutic strategies focused on reducing diabetes-associated complications, as well as the prevalence of obesity and smoking can improve patient outcomes and reduce HCC incidence. Future studies on the molecular background of metabolic alterations may help devise new therapeutic approaches aiming to improve the current management of MASLD-HCC.

Introduction: Recent data question the use of aspirin as a bedrock of antiplatelet therapy in patients with arterial diseases. There are controversies regarding the efficacy of aspirin therapy with respect to specific demographic characteristics, dose and formulations, benefit in primary prevention, and duration in secondary prevention. Importantly, to balance the ischemic benefits and the risk of excessive bleeding following a coronary event, recent studies have investigated strategies to discontinue aspirin therapy and continue with P2Y₁₂ receptor inhibitor monotherapy. However, the precise time when to discontinue aspirin is still unresolved.

Areas covered: Evidence from recent studies evaluating the role of aspirin in primary and secondary prevention studies was collected from a selective literature search. In this review, the authors discuss current recommendations, large-scale studies of aspirin therapy, controversies, and potential future opportunities for aspirin therapy.

Expert opinion: With the new evidence showing lower bleeding risk with aspirin-free strategies in both primary and secondary prevention studies, the role of aspirin is being revaluated with P2Y₁₂ receptor inhibitor monotherapy. The potential benefits of novel aspirin formulations and alternative delivery methods, such as inhaled aspirin, are undergoing much-needed investigation with the goal of optimizing care for a wide range of patients.

Introduction: Over a half century ago, a component of glucagon was found to have potent gastrointestinal effects. Shortly after proglucagon was sequenced, its component peptides were characterized, and glucagon-like polypeptide-2 (GLP-2) was noted to have the most potent intestinotrophic properties improving fluid and electrolyte balance in experimental animals and humans.

Areas covered: Glucagon-like polypeptide-1 (GLP-1) slows small intestinal motility more effectively, but its intestinotrophic properties are weaker. GLP-2's properties prompted study of its effects upon function of the surgically foreshortened small intestine, but its short half-life limited its usefulness, but the subsequent discovery that substitution of glycine for alanine at the second position of the molecule's N-terminus could lengthen its half-life to 2.5 hours, established efficacy in short bowel management with a single daily subcutaneous injection. Both adult and pediatric studies have shown reduced parenteral nutrition requirements and establishment of enteral autonomy for some patients. More recently, ultralong acting GLP-2 analogs with half-lives of 70-80 hours can improve gastrointestinal function in surgically foreshortened bowel with only one injection every three to seven days.

Expert opinion: Future research is likely to focus upon the potential complementary role of GLP-1 and GLP-2 in treating short bowel syndrome.

Introduction: Candida species produce a wide array of infections ranging from mucocutaneous to systemic infections. Candida albicans remains the most common species identified, however the non-albicans Candida species have continued to increase as the diagnosis and therapeutic regimens have progressed.

Areas covered: This review with discuss the various Candida species, especially the non-albicans species, some of the important mechanisms of resistance, and newer in vitro and clinical studies describing the recent and novel antifungal options such as rezafungin, ibrexafungerp, and oteseconazole, along with a novel antifungal, fosmanogepix.

Expert opinion: Initial antifungal therapy is frequently obsolete due to the expansion of antifungal resistance. This is especially true with C. glabrata, C. krusei, and most recently with C. auris. The newer and novel antifungals discussed here will add valuable tools to our antifungal armamentarium to be able to appropriately and adequately treat and manage these difficult infections. Each of the antifungals has unique and novel properties that will expand the arsenal useful to treat these fungal infections in the years to come.