Expert Review of Clinical Pharmacology最新文献

Introduction: Benzodiazepine derivatives and Z-drugs have traditionally been the cornerstone of pharmacological insomnia treatment. However, concerns regarding increased risks of falls, next-morning residual effects, dose tolerance, dependence, and withdrawal symptoms have prompted growing interest in alternative therapies.

Areas covered: This review critically assesses the effectiveness and challenges of lemborexant, a dual orexin receptor antagonist (DORA), in treating insomnia. It draws on current pharmacokinetic and clinical pharmacodynamic evidence, including data from phase 3 trials and meta-analyses.

Expert opinion: Lemborexant, with relative selectivity for the orexin receptor type 2, offers robust efficacy for both sleep initiation and maintenance. Its pharmacokinetic profile yields a quick onset and steep decline in plasma levels, helping minimize next-morning residual effects despite a long terminal half-life. Network meta-analyses demonstrate improvements in subjective and objective sleep measures, with lemborexant often ranking highest among hypnotics. Somnolence is the most common adverse event, while withdrawal symptoms, dependence, falls, cognitive impairment, and driving deficits are uncommon or comparable to placebo. Nightmares and sleep paralysis occur infrequently. Evidence supports its safe use in older adults and patients with obstructive sleep apnea or chronic obstructive pulmonary disease. Further research should address its role in psychiatric and medical comorbidities, and substance use disorders.

Introduction: Older people with dementia and mental health disorders frequently have co-occurring acute and chronic conditions resulting in polypharmacy. However, these populations are under-represented in clinical trials, and drug efficacy and tolerability are poorly understood. Electronic health records data represent valuable resources to investigate medication safety.

Areas covered: This report outlines the complexity of pharmacotherapy in late life and the key factors that need to be taken into consideration. In relation to the impoverished evidence base to support prescribing, it considers the important potential role of electronic health records data resources in addressing this, particularly within the UK National Health Service (NHS). The different types of current NHS databases in specialist and primary care are discussed alongside research outputs using these resources related to pharmacotherapy in people with dementia and/or late life mental disorders.

Expert opinion: NHS databases have particular value because of comprehensive catchment-based care provided by mental health and dementia diagnostic services and detailed long-term prescribing data captured in primary care. However, care for these disorders is usually delivered across multiple sectors with differing strengths and limitations in information availability and more work is needed in improving linked data infrastructures.

Background: Drug-drug interaction (DDI) is a global health concern affecting patient safety and treatment outcomes. Large language models (LLMs), such as ChatGPT, offer accessible alternatives; however, their effectiveness in DDI analysis remains unclear. This review evaluates the current evidence on the performance of LLM-based chatbots in identifying DDIs.

Methods: A PRISMA-compliant systematic review (PROSPERO: CRD420251020360) was conducted using PubMed, Scopus, and Web of Science (studies published between 1 January 2015, and 31 March 2025). Eligible studies included those using publicly accessible LLM chatbots for DDI detection.

Results: Nine studies (2023-2025) evaluated publicly accessible LLM chatbots, including ChatGPT, Bing AI, and Google Bard, for DDI identification. Methods varied from patient-level polypharmacy screening to single-drug checks and case vignettes. Chatbot performance was inconsistent: ChatGPT identified many potential DDIs, with ChatGPT-4.0 generally identifying more potential DDIs, but with variable accuracy, while Bing AI and Google Bard were less reliable.

Conclusion: Publicly accessible LLM chatbots demonstrate variable and partial effectiveness in detecting DDIs. There is a clear need to develop dedicated, freely available chatbots designed specifically for DDI identification. Future research should focus on standardizing evaluation methods and expanding access to improve medication safety in clinical practice.

Prospero: CRD420251020360.

Introduction: Chronic lymphocytic leukemia (CLL) primarily affects older adults, with a median age at diagnosis around 70 years. While targeted therapies have improved outcomes, treatment decisions in the elderly are complicated by comorbidities, fraility, and underrepresentation in clinical trials.

Areas covered: This review integrates geriatric oncology principles with therapeutic evidence to guide management of older adults with CLL. It summarizes frontline and relapsed/refractory strategies, drawing from landmark trials and real-world studies, and incorporates consensus on frailty assessment, polypharmacy, cardiovascular risk, and supportive care. Novel agents and treatment approaches are discussed in the context of functional status, patient preference, and quality of life, offering a practical age-adapted framework not addressed in prior reviews.

Expert opinion: While modern therapies allow longer survival with improved tolerability, several controversies remain. One challenge is managing patients with borderline fitness - those not formally frail yet with significant comorbidities or organ dysfunction. Another is sequencing after intolerance or progression on both BTK and BCL2 inhibitors, where evidence is sparse. Emerging options such as non-covalent BTK inhibitors, bispecific antibodies, and CAR-T hold promise, but their role in older or frail patients is unclear. Future age-adapted trials and biomarker-driven strategies are needed to balance survival with quality of life.

Introduction: Pharmacogenetic (PGx) testing remains widely underutilized despite strong evidence of genetic contributions to drug response and the availability of guidelines for integrating results into prescribing decisions. Challenges hindering PGx implementation include concerns about test reimbursement, knowledge gaps among patients and providers, and difficulty with effectively incorporating PGx data into the electronic health record (EHR). Our institution was an early adopter of PGx testing, with testing and clinical decision support available to guide multiple drug therapies, including clopidogrel, antidepressants, tacrolimus, and fluoropyrimidines.

Areas covered: This paper describes challenges our team and others have faced with PGx implementation and how we have addressed challenges common across implementations and those unique to specific gene-drug pairs.

Expert opinion: While we have demonstrated feasible solutions to overcome many implementation challenges, several key obstacles remain, including limited reimbursement for PGx testing as well as for pharmacist time in providing PGx consultations, challenges with EHR integration and portability of results, and demands for outcomes data. We anticipate broader implementation with legislative efforts to support reimbursement for testing and consultation. EHR vendors are also taking steps to better handle PGx data. Addressing genetic exceptionalism is particularly challenging but ultimately important for broad acceptance of PGx testing.

Introduction: Dementia with Lewy Bodies (DLB) is the second most common cause of neurodegenerative dementia after Alzheimer's disease, characterized by a complex combination of cognitive, neuropsychiatric, motor, autonomic, and sleep-related symptoms. Symptom fluctuation, polypharmacy risks, and high sensitivity to commonly used drugs present unique challenges for management.

Areas covered: This review provides a comprehensive overview of the symptomatic management of DLB, organized by clinical domains. It critically evaluates current pharmacological and non-pharmacological treatment strategies for cognitive impairment, hallucinations, parkinsonism, autonomic dysfunction, and sleep disturbances. Evidence is drawn from clinical trials, meta-analyses, and extrapolated findings from related disorders such as Alzheimer's disease and Parkinson's disease.

Expert opinion: Effective DLB management requires an individualized, symptom-prioritized approach that carefully balances therapeutic benefit with potential adverse effects, particularly given the high risk of antipsychotic sensitivity and treatment-induced worsening of symptoms. Despite recent progress, evidence remains sparse for many symptom domains. Greater investment in DLB-specific clinical trials and development of targeted therapies is urgently needed to improve patient outcomes.