Expert Review of Neurotherapeutics最新文献

Introduction: Anxiety disorders are among the most common co-occurring mental health conditions for autistic youth. While sometimes challenging to recognize, symptoms of anxiety can cause significant distress, functional impairment, and lead to a reduced quality of life. Thus, the effective treatment of co-occurring anxiety among autistic youth has considerable clinical importance. Cognitive behavioral therapy (CBT) has been shown to effectively treat clinically significant anxiety among children and adolescents, with specific modifications made to address challenges that often accompany autism spectrum disorders (ASD).

Areas covered: The authors have based this article on a comprehensive literature search that identified the extant evidence-based literature on CBT for anxiety among autistic youth in randomized controlled trials (RCTs). This review identified and synthesized modifications used to enhance treatment engagement and therapeutic efficacy.

Expert opinion: There are several evidence-based CBT protocols for autistic youth with anxiety disorders which include key modifications. Given the limited training opportunities in CBT for autistic youth, these protocol provide an initial framework for therapists to use when implementing CBT to treat anxiety disorders among autistic youth. It can also provide a path forward for personalized treatment approaches among this vulnerable and underserved population, as well as future directions for treatment.

Introduction: Major depressive disorder (MDD) is a leading cause of disability and is frequently associated with chronic comorbidities, including cardiovascular, neurological, psychiatric, and systemic diseases. Selecting an appropriate antidepressant is crucial, as some agents may present cardiovascular risks such as QTc prolongation, blood pressure alterations, bleeding tendencies, and drug interactions.

Areas covered: This consensus evaluates the cardiovascular safety of vortioxetine in clinically vulnerable patients with MDD and multiple comorbidities, including cardiovascular disease, hypertension, diabetes, obesity, cerebrovascular disorders, and other neurological or psychiatric conditions. A targeted literature search was conducted in PubMed and Google Scholar for studies published between 2015 and 2024 using search terms related to "vortioxetine," "major depressive disorder," "cardiovascular comorbidity," "efficacy," and "safety." The analysis integrates available evidence on efficacy, tolerability, and cardiovascular outcomes.

Expert opinion: Vortioxetine demonstrates antidepressant efficacy and a favourable cardiovascular profile. It is not associated with QTc prolongation, arrhythmic risk, or significant effects on blood pressure, heart rate, or platelet aggregation. Its limited involvement in cytochrome P450 metabolism reduces the potential for drug interactions. Overall, vortioxetine offers an optimal balance of efficacy and safety for patients with MDD and chronic comorbidities. A multidisciplinary approach remains essential to improve treatment outcomes and quality of life.

Introduction: Social anxiety disorder (SAD) is a common and disabling mental disorder that follows a chronic course unless it is treated with effective treatments. This systematic review examines randomized controlled trials (RCTs) of pharmacological treatments for adults with SAD published since 2015.

Methods: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Search was conducted on PubMed, Scopus, Web of Science, and PsycINFO. Risk of bias of the included studies was assessed using the Cochrane risk of bias tool for randomized trials.

Results: Eighteen RCTs were included. Selective serotonin reuptake inhibitors (SSRIs) were the most investigated pharmacological intervention, either as monotherapy or in combination with cognitive behavioral therapy (CBT). More recent drugs show promising results include cannabidiol and d-cycloserine.

Conclusion: When CBT is unavailable, SSRIs are the first-line pharmacological treatment for SAD based on current evidence. However, response rates vary substantially. We recommend a personalized approach that includes patient preference and treatment accessibility.

Background: This study assessed neurologists' and psychiatrists' experience with and perceptions of tetrabenazine (TBZ) when treating patients with tardive dyskinesia (TD) and Huntington disease (HD)-related chorea.

Research design and methods: Neurologists and psychiatrists from Australia and Israel who manage TD, and neurologists from Australia, Israel, and South Korea who manage HD-related chorea, answered 20-minute anonymous online questionnaires.

Results: A total of 72 neurologists and psychiatrists managing patients with TD and 24 neurologists managing patients with HD-related chorea were included. Among physicians who had experience with TBZ (TD, n = 62; HD, n = 20), most (61%; 80%) were moderately satisfied with TBZ for treatment of TD/HD-related chorea, some were dissatisfied (23%; 10%), and only 17% and 10% were very/extremely satisfied. Additionally, 18% and 25% reported that they were often/almost always unable to titrate TBZ to optimal doses because of side effects and 24% and 15% reported that side effects often/almost always led to TBZ discontinuation.

Conclusion: Although most physicians were moderately satisfied with TBZ, they also reported that TBZ side effects prevented reaching optimal clinical effectiveness and often led to discontinuation, suggesting a need for additional effective treatment options with favorable benefit-risk profiles for TD and HD-related chorea.

Introduction: Parkinson's disease (PD) exhibits distinct phenotypes with specific pathophysiological features. Their definition is essential to inform therapeutic choices and trials design.

Areas covered: We searched in September 2025 PubMed/MEDLINE, Scopus, and Web of Science to review current PD stratifications strategies based on clinical, tissue, and imaging biomarkers, highlighting their specific strengths and limitations. We provide an overview of the proposed pathophysiological mechanisms underlying distinct phenotypes and the open challenges in the field.

Expert opinion: Subtyping of PD based on clinical phenotype is rapidly evolving, driven by advances in understanding its pathological mechanisms and clinical heterogeneity. Identifying distinct PD phenotypes is essential to deliver personalized care and optimize clinical trial design, particularly for disease-modifying therapies. Neurotransmitter-based subtyping (cholinergic/noradrenergic/serotonergic) provides a biologically grounded framework that partially overlaps with anatomical models such as the brain-first/body-first distinction. However, validity of such models is also controversial, especially in more advanced stages of PD where many pathways merge. Integrating multimodal data, including clinical/imaging/biomarker/genetic measures, is crucial to improve stratification accuracy and account for comorbidities/copathology. Future progress relies on hypothesis-supervised data-driven approaches, longitudinal validation, and globally inclusive cohorts to achieve robust, biologically informed, and clinically meaningful PD subtyping.

Introduction: Restless Legs Syndrome (RLS) is a sensorimotor disorder linked to brain iron deficiency and dopaminergic dysfunction. Increasing evidence suggests that alterations in adenosine signaling may represent the missing link connecting dopaminergic and glutamatergic abnormalities. The 'adenosine hypothesis' proposes that brain iron deficiency induces a hypoadenosinergic state, primarily through adenosine A₁ receptor downregulation, resulting in cortical hyperexcitability, hyperarousal, and periodic limb movements.

Areas covered: This critical perspective examines experimental, neurophysiological, and clinicaldata supporting the adenosine hypothesis of RLS. Findings from animal models demonstrate altered A₁/A_2A receptor balance in cortico-striatal terminals, promoting glutamatergic hyperactivity. In particular, neurophysiological studies further support the adenosine hypothesis, highlighting a pattern of cortical hyperexcitability and impaired inhibitory control in RLS. In this context, preliminary clinical trials with dipyridamole, an equilibrative nucleoside transporter inhibitor that enhances extracellular adenosine, showed symptomatic improvement, supporting adenosinergic enhancement as a therapeutic approach.

Expert opinion: The adenosine hypothesis provides an integrative framework uniting dopaminergic, glutamatergic, and iron-related mechanisms in RLS. Targeting adenosine transmission could complement existing therapies and mitigate augmentation. Future research should prioritize receptor-selective ligands, multimodal biomarkers, and controlled trials to translate this hypothesis into mechanism-based neurotherapeutic strategies.

Introduction: Perry syndrome (PS) is a rare, inherited neurodegenerative disorder caused by mutations in the DCTN1 gene. It is characterized by parkinsonism, neuropsychiatric symptoms, central hypoventilation, and progressive weight loss, typically leading to a rapid disease course and early death. As genetic testing becomes more widespread, PS is increasingly diagnosed, and its clinical spectrum is expanding.

Areas covered: The authors conducted a comprehensive search of public databases through September 2025 to identify original research, conference proceedings, and book chapters related to Perry syndrome. This review summarizes the current understanding of the disease, including its clinical, pathologic, and genetic aspects. The authors also provide practical recommendations for managing symptoms, particularly through optimization of dopaminergic therapy, antidepressive treatment, and noninvasive or invasive ventilation support, which can greatly improve quality of life and extend survival.

Expert opinion: Although there are currently no approved disease-modifying therapies for PS, recent research into the underlying pathology, such as TDP-43 and axonal transport dysfunction, offers promising targets for future treatments. A new staging system for PS is recommended for PS, which will help to standardize the clinical assessment of PS and guide therapeutic decision-making.

Introduction: The ketogenic diet as a potential treatment for Alzheimer's disease (AD) has been investigated in several controlled trials. This topic is significant because of the limited nature of current interventions for AD, and the increasing recognition that lifestyle interventions may be important for reducing the risk of AD. The ketogenic diet is one of the few lifestyle interventions that has the potential to be beneficial after diagnosis.

Areas covered: In this narrative review, the authors discuss the biological plausibility of how a ketogenic diet may improve amyloid burden and reduce neuroinflammation by providing an alternative energy source. They review relevant meta-analyses, systematic reviews, and controlled trials to investigate this diet in people diagnosed with AD. To this end, the authors used PubMed to search for appropriate systematic reviews and human trials, and closely examined the bibliographies of these papers to find trials potentially missed in their initial search.

Expert opinion: More research is needed before a ketogenic diet could be broadly recommended in patients diagnosed with AD. However, to the extent a treatment effect has been demonstrated, it is comparable to some pharmaceutical interventions in AD. Challenges that remain include demonstrating improvement in quality of life, improving adherence, and standardizing ketogenic therapies.

Introduction: Migraine is among the most disabling neurological disorders worldwide and preventive treatment remains a cornerstone for reducing disease burden. Recent advances in mechanism-based therapies have positioned calcitonin gene-related peptide (CGRP) and its main receptor as central targets for migraine prophylaxis.

Areas covered: This updated narrative overview summarizes the pharmacological profile, clinical efficacy, safety and regulatory status of rimegepant, integrating evidence published through 2025 and highlighting emerging real-world and clinical trends. Relevant literature was identified through searches in PubMed/MEDLINE and Scopus (last search: 19 November 2025) using predefined combinations of terms related to rimegepant and migraine. The review also examines emerging concepts such as situational prevention, potential combination approaches with traditional or novel preventives and exploratory use in other CGRP-mediated headache disorders.

Expert opinion: Rimegepant represents a significant addition to migraine prophylaxis by offering a flexible and well-tolerated option that bridges acute and preventive care. Its role may expand through rational combinations and investigation in other headache disorders. Persistence and long-term safety require careful monitoring, and reimbursement frameworks will determine its future clinical adoption.