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: 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: Alpha-1 adrenergic receptor antagonist (α1-ARA) are well established treatment for benign prostatic hyperplasia (BPH)-associated lower urinary tract symptoms (LUTS). Since BPH and erectile dysfunction (ED) are commonly concomitant conditions, the importance of addressing the potential role of α1-ARA in patients with ED is rising.

Methods: We systemically reviewed literature for studies that assessed erectile function (EF) indices in relation to α1-ARA use. All types of comparisons were included.

Results: Out of 1915 records, 21 articles have been included. All articles suffered high risk of bias. α1-ARA showed a significant improvement in EF in comparison to baseline and placebo. Some α1-ARA are more erectogenic than others. Combined therapy with phosphodiesterase-5 inhibitors improved EF better than either alone. Factors like associated lower urinary symptoms, dose, duration of therapy modify α1-ARA effects on EF.

Conclusion: Αlpha1-ARAs have a potential role in improving EF in subjective and objective scales. However, the available evidence is extracted from studies on patients with other indications for α1-ARAs, particularly BPH-related LUTS. Further investigations should target patients with ED only to precisely identify their clinical utility.

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: 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: 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: Despite a rising incidence, biliary tract cancers (BTCs) are still considered a rare tumor entity. The disease's subtle clinical presentation and lack of effective early detection strategies often lead to a diagnosis at an advanced or unresectable stage, where curative options are limited.

Areas covered: This review provides an overview of current systemic therapies and emerging novel approaches for BTC. For decades, the combination of gemcitabine with cisplatin (GemCis) has been the standard of care for palliative treatment. However, since 2020, the diagnostic and therapeutic landscape for BTC has evolved considerably, not only in the first-line setting but also beyond, driven by the development of clinical trials exploring immunotherapy and molecularly targeted agents. Due to the high frequency of targetable genetic alterations in BTC patients, there is a growing emphasis on obtaining tissue or liquid biopsy samples to identify markers like microsatellite instability and other actionable oncogenic driver genes.

Expert opinion: Early initiation of systemic therapies in combination with multimodal approaches is essential for maximizing survival outcomes in patients with BTC.

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.