Expert Opinion on Pharmacotherapy最新文献

Introduction: Substance use disorders (SUDs) are a public health issue, with only some having FDA-approved indicated treatments and these having high attrition. Consequently, there has been interest in novel interventions (e.g. psychedelics that target 5-HT2A receptors) with some promising results. In this narrative review, we aim to focus on the role of the 5-HT2A receptors on the effectiveness of the treatment of SUDs.

Areas covered: We evaluated the clinical evidence of the treatment of SUDs with non-psychedelic medications with a primary affinity for the 5-HT2A receptor.

Expert opinion: The reviewed literature showed some positive effects on craving and abstinence but, overall, results were mixed. Comparison of this work with work on psychedelic agents suggests that mixed results are not unique to non-psychedelic agents. Both psychedelic and non-psychedelic drugs with 5-HT2A affinity are not exclusively selective for 5-HT2A receptors. The observation that most agents reviewed are 5-HT2A receptor antagonists instead of agonists and that psychedelics (typically 5-HT2A receptor agonists) may have more homogenous positive results gives more support to 5-HT2A receptor agonists as a promising group for treating SUDs. Mechanisms may target a common denominator across SUDs (e.g. chronic hypodopaminergic states).

Introduction: Complicated urinary tract infections (cUTIs) represent a significant clinical challenge due to their association with sepsis, high morbidity and mortality, and an increased risk of recurrence and chronic infection. Effective management requires prompt, targeted interventions.

Areas covered: This review highlights the importance of early, targeted antibiotic therapy based on local resistance profiles, patient-specific factors, and pharmacokinetic/pharmacodynamic considerations. We examined emerging and existing antibiotics, including beta-lactams, fluoroquinolones, aminoglycosides, and beta-lactamase inhibitor combinations, which show potential against multidrug-resistant organisms (MDRO) linked to cUTI. Additionally, we propose revisiting the broad definition of cUTI to promote a more pragmatic approach that minimizes unnecessary antibiotic use and hospitalization.

Expert opinion: Current evidence underscores the need for antimicrobial stewardship, precise diagnostics, and innovative therapies to address cUTI while mitigating antimicrobial resistance. A targeted, patient-centered approach is essential to optimize outcomes and reduce the burden of resistant infections.

Introduction: Meibomian Gland Dysfunction (MGD) represents the most common cause of dry eye disease (DED). Traditional treatments mainly rely on heating and liquifying the meibum to favor its expression. However, recent knowledge advances have led to the development of novel therapies specifically designed for patients with MGD.

Areas covered: Literature search was conducted on current and novel treatments for MGD. Conventional treatment strategies, non-pharmacological approved device-based therapies, approved dry eye therapies and both recently approved and emerging pharmacological treatments specifically designed to address MGD are discussed.

Expert opinion: The better understanding of MGD and DED pathophysiology has allowed to develop drugs able to target the primary mechanisms of the disease. Miebo has been the first FDA approved drug for patients with DED associated with MGD and its ability to reduce the tear film layer evaporation rate and the minimal impact on the quality of vision are important innovations. Great expectations also accompany the phase 3 study of AZR-MD-001, understood to be a keratolytic and lipogenic agent able to improve meibum quantity and quality. The chance to specifically target MGD represents an important step forward and will allow more tailored treatment for each type of ocular surface disease.

Introduction: Lipid-lowering therapies are well established for the treatment of cardiovascular disease (CVD). Historically monotherapy studies have been performed, but the introduction of statins has led to these drugs being recognized as baseline therapies and to the investigation of combination therapy of both older and newer medications with them.

Areas covered: Surrogate marker studies have shown additive effects on LDL-C, triglycerides and HDL-C of combination therapies with statins and these have extended to lipoprotein (a). Imaging studies have often shown benefits paralleling lipid studies. However, outcome studies have failed to show added benefits with niacin or fibrates while confirming the benefits of ezetimibe, bempedoic acid and proprotein convertase subtilisin kexin-9 (PCSK-9) inhibitors and icosapent ethyl.

Expert opinion: Combination therapy for LDL-C in dual combinations is well validated. Data for intervention on triglycerides is limited to icosapent ethyl, but this may exert effects independent of lipids. New drugs targeting triglycerides through apolipoprotein C3 and angiopoietin-like peptides are in development. Studies on combination therapy raising HDL-C have generally disappointed, though cholesterol ester transfer protein (CETP) inhibition remains a target. Lipoprotein (a) is recognized as a CVD risk factor and effective therapies are in development but results on CVD events are lacking.

Introduction: Alcohol use disorder (AUD) is prevalent and recognized as a chronic, relapsing disorder. Even though effective treatment options are available, AUD is strongly undertreated. As adjuvant treatment strategies accompanying psychosocial treatments, pharmacological strategies can increase the efficacy of AUD treatment options.

Areas covered: After giving a brief update of epidemiology, neurobiology and treatment rationales for AUD, the review outlines pharmacological interventions against the background of current evidence. These include approved substances like naltrexone, nalmefene, acamprosate and disulfiram, second line medications like topiramate, baclofen and varenicline and novel approaches like hallucinogens. The review refers to the primary database on pharmacotherapies for AUD and to findings from pairwise and network meta-analyses. It illustrates effects of pharmacotherapies for AUD on different outcomes and assesses risks and benefits of treatment strategies. Search has been conducted in PubMed using the substance name or related categories (such as anti-craving or relapse prevention) as key words.

Expert opinion: Improved understanding of AUDs neurocircuitry expands the range of available pharmacotherapeutic strategies for supporting abstinence and drinking reduction. Pharmacotherapies for AUD can be improved by understanding differences in treatment response. Matching different treatment approaches to individual needs can challenge the view of alcohol dependence as a lifelong disorder.

Introduction: Overactive bladder (OAB) is a prevalent disorder with a significant impact on quality of life. The pathophysiology of OAB is multifactorial and the majority of patients will require treatment with multiple therapies across the course of their disease. First line treatments include bladder retraining, fluid advice and pelvic floor muscle training. Following this, patients may be offered treatment with anticholinergic and β₃ agonist medications. Anticholinergics are known to have high rates of discontinuation due to side effects and there are concerns regarding anticholinergic load and its impact on cognitive function in older adults.

Areas covered: This paper aims to discuss the current and emerging treatment options available for patients who suffer from OAB.

Expert opinion: The management of OAB in the clinical setting remains challenging. The goal of newer pharmacotherapies in OAB would be treatment that provides long term symptomatic relief with minimal side effects and an improved quality of life. The future of OAB research is promising and should consider the implications of the gut-bladder axis, regenerative medicine, biomarkers and the role of digital health.

Introduction: Endometriosis is a chronic inflammatory estrogen-dependent disease affecting 10% of women worldwide leading to chronic pelvic pain and infertility which may be treated clinically or surgically.

Areas covered: Current literature was reviewed using the keywords 'gonadotropin releasing hormone agonists (GnRHa),' 'endometriosis,' 'infertility' and 'chronic pelvic pain.' Relevant papers prioritizing randomized controlled clinical trials (RCT), systematic reviews, meta-analyses, as well as international guidelines were evaluated.

Expert opinion: Available options for relieving endometriosis-associated pain include GnRHa, progestagens, and combined oral contraceptives, all of which block menstruation to control symptoms without curing the disease. GnRHa administration decreases pain and symptom recurrence after surgical treatment, but side effects and costs limit its use. Published studies to test its effectiveness in easing endometriosis-associated pain are heterogeneous, consider different outcomes with no long-term results. Drug choice should be individualized considering the side-effect profile, tolerability, costs, risks, and benefits as one size does not fit all. As we wait for the development of an ideal pharmacological agents, GnRHa with an add-back regimen remains a second-line option to alleviate the painful symptoms in women with endometriosis. Endometriosis management should consider the systemic nature of the disease and the complexity involved in the pathogenesis of symptoms.

Introduction: Type 1 diabetes is a unique autoimmune attack on the β cell of the pancreatic islet resulting in progressive destruction of these cells and as a result the ability of the body to maintain insulin production. The consequences of insulin deficiency are very severe, and the disease was fatal prior to the ability to extract insulin from animal pancreas in 1921. We review progress in the treatment of childhood type 1 diabetes over the past 100 years.

Areas covered: We used PubMed and standard search engines to search for the evolution of diagnosis and treatment of type 1 diabetes.

Expert opinion: Insulin replacement proved lifesaving for children afflicted with type 1 diabetes. However, it was observed that these children suffered from microvascular and large vessel disease. The Diabetes Control and Complications Trial (DCCT) with its extension Epidemiology of Diabetes Interventions and Complications Trial (EDIC) proved that control of blood glucose as close to normal as possible could prevent these diabetes-related conditions. Many formuations of insulin with varying onset and duration of action have been developed; yet normalization of glucose levels is difficult due to hypoglycemic events. There is continued progress toward that goal.

Introduction: The PI3K pathway is crucial in breast cancer (BC), influencing cell survival, growth, and metabolism, with AKT playing a central role in treatment resistance. This pathway's involvement in breast carcinogenesis and its link to treatment resistance underscores the significance of targeting it in BC therapy. PI3K-pathway inhibitors offer new therapeutic avenues but bring challenges, especially due to toxicity issues that hinder their development.

Areas covered: This review discusses the PI3K-pathway inhibitors used in BC, highlighting emerging, innovative strategies.

Expert opinion: The introduction of mTOR inhibitors marked a key step in tackling hormone receptor-positive (HR+) BC, targeting endocrine resistance. However, toxicity concerns remain, especially with PIK3CA and AKT inhibitors. Selective PI3K-targeted agents aim to reduce off-target toxicity, enhancing patient adherence and control over the disease. New compounds employing allosteric mechanisms may further limit adverse effects and allow safer combination therapies, previously limited by toxicity. Advancements in dosing strategies focus on patient-centered outcomes, and synergistic agents are essential in advancing AKT-pathway inhibition, paving the way for a new phase in HR+ BC treatment.