Expert Review of Clinical Pharmacology最新文献

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.

Introduction: Statins are strongly recommended to reduce major adverse cardiovascular events, making them widely prescribed by health-care providers. Despite this, statins are underutilized in older adults (≥65 years of age), partially related to the fear of adverse effects. Statin associated muscle symptoms (SAMS) are commonly cited as a reason for statin discontinuation.

Areas covered: This review discusses the incidence, contributing factors, and clinical trial data surrounding SAMS in older adults. An approach to treating older adults with SAMS is proposed.

Expert opinion: Treating older adults who experience SAMS is challenging. Utilizing shared decision-making, patients who experience SAMS may be successfully rechallenged with a statin. If a patient is unable to tolerate a statin, non-statin therapeutic options can be considered to reduce cholesterol and improve cardiovascular outcomes.

Introduction: Several clinical trials have demonstrated that chemotherapy contributes to prolonged survival in patients with previously treated advanced gastric cancer (AGC).

Areas covered: Currently, cytotoxic agents with established efficacy for previously treated AGC include paclitaxel (PTX), irinotecan (IRI), and trifluridine/tipiracil (FTD/TPI), while the anti-vascular endothelial growth factor(VEGF) agent ramucirumab (RAM) has also shown efficacy. Pembrolizumab is indicated for AGC with microsatellite instability-high (MSI-H) or high tumor mutational burden (TMB). For human epidermal growth factor receptor 2 (HER2)-positive previously treated AGC, trastuzumab deruxtecan (T-DXd) has emerged as the first molecular targeted therapy. Additionally, claudin-18 isoform 2 (CLDN18.2)-targeting antibody therapy has been established as a first-line treatment, with numerous ongoing clinical trials in later-line settings. Other promising molecular targets include trophoblast cell surface antigen 2 (TROP2), cytoplasmic activation/proliferation-associated protein 1(CAPRIN-1), and KRAS. Furthermore, innovative therapeutic approaches such as antibody-drug conjugates (ADCs), bispecific antibodies (BsAbs), and chimeric antigen receptor T-cell (CAR-T) therapy are being developed. This review summarizes the historical and established evidence from clinical trials on previously treated AGC and discusses ongoing clinical trials and future perspectives in treatment development, with a focus on targeted therapies.

Expert opinion: Biomarker-driven treatment is expected to become the mainstream approach in the future.

Introduction: Every year more than 50 million people in the world experience a traumatic brain injury (TBI). In its more severe form the mortality is high, and survivors can be very disabled. Nevertheless, there are currently no approved pharmacological treatments that definitely improve the prognosis in humans, and given the consistently disappointing results, pharmaceutical companies are reluctant to invest further.

Areas covered: We reviewed relevant PubMed-indexed studies on pharmacological trials conducted during the acute phase of TBI. The potential reasons for the observed lack of efficacy are discussed, including the vast heterogeneity within the TBI population, the limitations of randomization in balancing prognostic factors, and challenges posed by current clinical endpoints used to assess treatment outcomes.

Expert opinion: The search for new pharmacological treatments of TBI patients must continue, but a change of paradigm should be accepted by scientists and regulatory authorities. In the unique context of TBI patients, randomization and patients stratification are not sufficient to create homogeneous and comparable groups. Current clinical outcomes are too influenced by variables and too 'hard.' Alternative endpoints, i.e. relevant pathophysiological variables (e.g. ICP, biomarkers, MRI), if accepted could encourage pharmaceutical companies to develop drugs in TBI.